Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

ATM (ataxia telangiectasia mutated)

Written2021-04Jean Loup Huret
jean-loup.huret@atlasgeneticsoncology.org
This article is an update of :
2016-10Yossi Shiloh
The David and Inez Myers Chair in Cancer Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; yossih@post.tau.ac.il
2002-11Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
1999-10Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
1998-04Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Abstract Review on ATM, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords Ataxia telangiectasia ; Cerebellar ataxia; Telangiectasia; Immunodeficiency; T- cell malignancies; B-cell malignancies; Carcinomas; Senescence; Chromosome instability syndrome; DNA double-strand breaks; Translocation; Oxidative stress; Homeostasis; ATM; chromosome.

(Note : for Links provided by Atlas : click)

Identity

HGNC (Hugo) ATM
HGNC Alias symbTEL1
TELO1
HGNC Alias nameTEL1, telomere maintenance 1, homolog (S. cerevisiae)
HGNC Previous nameATA
 ATDC
 ATC
 ATD
HGNC Previous nameataxia telangiectasia mutated (includes complementation groups A, C and D)
 ataxia telangiectasia mutated
LocusID (NCBI) 472
Atlas_Id 123
Location 11q22.3  [Link to chromosome band 11q22]
Location_base_pair Starts at 108223529 and ends at 108229364 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping ATM.png]
Local_order SLN, SLC35F2, RAB39A, CUL5, ACAT1, NPAT, ATM, C11orf65, POGLUT3, EXPH5, DDX10
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ATM (11q22.3)::ASPH (8q12.3)ATM (11q22.3)::ATM (11q22.3)ATP6V1C2 (2p25.1)::ATM (11q22.3)
CUX1 (7q22.1)::ATM (11q22.3)JARID2 (6p22.3)::ATM (11q22.3)
Note This 2021 update only concerns 1- details on the DNA, the protein domains and amino acids sequence, and 2- data on diseases where ATM is implicated. The whole protein function chapter remains the 2016 review written by Yossi Shiloh
See also, in Deep Insight section: Ataxia-Telangiectasia and variants.

DNA/RNA

 
  ATM (11q22.3) in normal cells: PAC 1053F10 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Description Transcript (hg38) including UTRs: chr11:108,222,832-108,369,099, size: 146,268 on plus strand; coding region: chr11:108,227,625-108,365,508 Size: 137,884 according to UCSC. ATM has 30 transcripts (splice variants). The canonical form (ATM-003) is the longest, with 64 exons: 12954 bp --> 3056 amino acids (aa). Most transcripts (9 of 11) code for short (93 to 168aa) proteins which contain the TAN domain only. One transcript (ATM-001) with 27 exons, codes for a 1,369 aa protein.
Transcription Table 1. ATM exons and transcription - Canonical form (NextProt Exons). Coding Positions from 108,227,625 to 108,365,505 [length: 137,881 bp].
IdentifierPosition on geneLength
Amino acids
ENSE00002185659633 - 70371
ENSE000021517402301 - 238888
ENSE000037429335112 - 5213102
Met1 - Lys24
ENSE000037250825293 - 5405113
Lys25 - Arg62
ENSE000037448056695 - 6840146
Arg62 - Arg111
ENSE0000166708813187 - 13351165
Arg111 - Glu166
ENSE0000167071021470 - 21635166
Glu166 - Arg221
ENSE0000173959822305 - 22543239
Arg221 - Gly301
ENSE0000161729524481 - 24644164
Gly301 - Gln355
ENSE0000165281526450 - 26619170
Val356 - Trp412
ENSE0000165830628218 - 28589372
Trp412 - Cys536
ENSE0000163873129354 - 29548195
Cys536 - Ser601
ENSE0000165540630334 - 3042996
Ser601 - Cys633
ENSE0000159211631331 - 31556226
Cys633 - Glu708
ENSE0000177490033732 - 33857126
Ile709 - Lys750
ENSE0000172383534998 - 35123126
Ser751 - Lys792
ENSE0000176950936503 - 3659290
Lys793 - Leu822
ENSE0000171937844688 - 44859172
Ala823 - Gly880
ENSE0000359577045927 - 46126200
Gly880 - Met946
ENSE0000159192348581 - 4866383
Tyr947 - Ser974
ENSE0000176429648768 - 48923156
Ser974 - Trp1026
ENSE0000349173850049 - 5012476
Trp1026 - Glu1051
ENSE0000348412750239 - 50369131
Ala1052 - Arg1095
ENSE0000360575357008 - 57125118
Arg1095 - Met1134
ENSE0000161854358512 - 58685174
Ser1135 - Lys1192
ENSE0000176133860227 - 60396170
Val1193 - Arg1249
ENSE0000164961061744 - 61990247
Arg1249 - Gln1331
ENSE0000172896665117 - 65232116
Ile1332 - Gly1370
ENSE0000346919466494 - 66620127
Gly1370 - Pro1412
ENSE0000358103567119 - 67318200
Asp1413 - Arg1479
ENSE0000359867770136 - 70310175
Arg1479 - Gln1537
ENSE0000352949770830 - 70994165
Val1538 - Glu1592
ENSE0000355926472444 - 72576133
Glu1593 - Asp1637
ENSE0000348040674804 - 74899 96
Asp1637 - Glu1669
ENSE0000356558477231 - 77402172
Glu1669 - Cys1726
ENSE0000359011579165 - 79306142
Cys1726 - Lys1773
ENSE0000350806180370 - 80546177
Phe1774 - Glu1832
ENSE0000347209282192 - 82369178
Val1833 - Glu1892
ENSE0000347251785414 - 8550188
Glu1892 - Arg1921
ENSE0000359103487677 - 87832156
Arg1921 - Arg1973
ENSE0000345842789928 - 9001588
Arg1973 - Gln2002
ENSE0000361455293340 - 9342889
Asp2003 - Arg2032
ENSE0000355239193528 - 93630103
Arg2032 - Gln2066
ENSE0000352257794890 - 95038149
Ala2067 - Ser2116
ENSE0000368881997471 - 97575105
Ser2116 - Arg2151
ENSE0000364838998818 - 98937 120
Arg2151 - Arg2191
ENSE00003542516102827 - 103061235
Arg2191 - Gln2269
ENSE00003580001103575 - 103742168
Leu2270 - Ala2325
ENSE00003479049105162 - 105275114
Asn2326 - Lys2363
ENSE00003599084106538 - 106755218
Ala2364 - Arg2436
ENSE00003659411107731 - 107938208
Arg2436 - Lys2505
ENSE00003596787108961 - 109074114
Arg2506 - Asn2543
ENSE00003571052109396 - 109554159
Leu2544 - Glu2596
ENSE00003483502110279 - 110417139
Asp2597 - Lys2643
ENSE00003573212111403 - 11148583
Lys2643 - Lys2670
ENSE00003560896112486 - 112626141
Val2671 - Lys2717
ENSE00003666486113362 - 113478117
Gly2718 - Lys2756
ENSE00003611442120739 - 120888150
Val2757 - Met2806
ENSE00003671649123260 - 123425166
Glu2807 - Val2862
ENSE00003588344124796 - 12488287
Val2862 - Gly2891
ENSE00003609743131283 - 131397115
Gly2891 - Arg2929
ENSE00003638878132328 - 13239164
Arg2929 - Glu2950
ENSE00003502604142599 - 142735137
Val2951 - Ser2996
ENSE00002195058142842 - 1466193778
Ser2996 - Val3056

The ATM promotor is bi-directional and also directs the transcription of the NPAT gene.

Protein

 
  Figure 1: ATM amino acids sequence
Description This large polypeptide of 350 kDa and 3,056 residues bears a PI3 kinase signature within its carboxy-terminal catalytic site, but has the catalytic activity of a serine-threonine protein kinase. This motif is characteristic of a protein family of which ATM is a member - the PI-3 kinase-like protein kinases (PIKKs; Lovejoy et al., 2009; Baretić et al., 2014).
ATM can be divided in 2 parts: a N-solenoid and a FATKIN. The N-solenoid is made, from N-term, of a Spiral (aa 1-1160) and a Pincer ((aa 1161-1890), itself made of a N-pillar (aa 1161-1430), Bridge (aa 1431-1600), C-pillar (aa 1601-1680), Railing (aa 1681-1800), and Cap (aa 1801-1890). Following the N-solenoid is the FATKIN (aa 1891-3056). The FATKIN, consists of a FAT and the C-terminal kinase domain. The FATKIN can be divided into five domains: tetratricopeptide repeat domains TRD1 (aa 1903-2025), TRD2 (aa 2032 -2190), and TRD3 (aa 2195-2476); HRD (HEAT-repeats domain) (aa 2484-2612); and a kinase domain (aa 2618-3056). There are also a LST8-binding element (LBE, aa 2791-2829) and an activation loop (aa 2888-2910), see Figures 1 and 2 (Young et al., 2005; You et al., 2005; Bhatti et al., 2011; Baretic and Williams 2014; Cremona and Behrens 2014; Lau et al., 2016; Wang et al., 2016; Baretic et al., 2017; Baretic et al., 2019).
The main domains and motifs are, from N-term to C-term:
a TAN motif (aa 15-27 (located in 18-40 in UniProt)); a chromatin-association domain of ATM (amino acids 5-224); a nuclear localization signal: KRKK (aa 385-388), within aa 227–568; a leucine zipper (aa 1217-1239); a FAT domain (aa 1940-2566 according to UniProt; includes TRD1 to 3 and HRD, i.e. from aa 1903 to 2612 according to Baretic et al., 2017); a phosphatidylinositol 3- and 4-kinases signature 1 (aa 2716-2730 (UniProt)); a phosphatidylinositol 3- and 4-kinases signature 2 (aa 2855-2875 (UniProt)); and a FATC domain (aa 3024-3056 according to Baretic et al., 2017 and to UniProt).
The Spiral has roles in binding substrates, regulators, and adaptors. TAN is a motif which is conserved specifically in the Tel1/ATM subclass of the PIKKs (interPro). TAN motif (Tel1/ATM N-terminal or Telomere-length maintenance and DNA damage repair) contains a conserved (L/V/I)XXX(R/K)XX(E/D)RXXX(L/V/I) signature. In the case of ATM: LEHDRA TERKKEV (aa 15-27) The TAN motif plays a role in telomere length maintenance. FAT/FATC domain: The PI-kinase domain of members of the PIK-related family is made of a FAT (FRAP, ATM, TRRAP) domain and the C-terminal FATC domain (interPro). The FATC (FRAP, ATM, TRRAP C-terminal) domain is essential for the kinase activity. PI3/4-kinase (Phosphatidylinositol 3-/4-kinase, catalytic domain): Phosphatidylinositol 3-kinase (PI3-kinase) is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring (interPro). Leucine zipper: region required for dimerization mediating sequence-specific DNA-binding (interPro).
Other remarkable sites according to Prosite: (see Figure 2)
- Protein kinase C phosphorylation sites: aa 21, 39, 127, 151, 274, 305, 373, 475, 491, 554, 571, 616, 775, 791, 808, 917, 1037, 1104, 1179, 1487, 1558, 1769, 1770, 1857, 1880, 1905, 1990, 2058, 2134, 2146, 2194, 2242, 2264, 2329, 2434, 2438, 2513, 2608, 2611, 2640, 2685, 2745, 2754, 2761
- Casein kinase II phosphorylation sites: 127, 200, 274, 373, 403, 470, 515, 571, 629, 644, 646, 655, 710, 767, 837, 865, 891, 934, 1004, 1048, 1100, 1118, 1143, 1179, 1212, 1242, 1263, 1350, 1403, 1589, 1601, 1609, 1721, 1748, 1819, 1891, 1966, 1988, 1993, 2000, 2011, 2123, 2134, 2142, 2184, 2218, 2242, 2333, 2348, 2359, 2375, 2408, 2476, 2573, 2592, 2812, 2921, 2947, 2996
- cAMP- and cGMP-dependent protein kinase phosphorylation sites: 1923, 2751
- Tyrosine kinase phosphorylation sites: KcqEllnY (116-123),KtqEkgaY (296-303),RhgErtpY (447-454), KvsEtfgY (1196-1203), KevEgtsY (2117-2124), KrslEsvY (2160-2167), KksfEekY (2810-2817)
- N-glycosylation sites: 81, 272, 567, 591, 704, 765, 789, 1230, 1240, 1356, 1660, 1719, 1855, 2994, 3044
- N-myristoylation sites (role in membrane targeting): 134, 138, 301, 506, 558, 724, 774, 1016, 1302, 1456, 1458, 1672, 1817, 1925, 1980, 2020, 2063, 2342, 2369, 2678, 2917, 3019, 3023, 3029
Amino acids 90 to 97 interact with TP53, BRCA1, and STK11. The binding site for NBS1 maps to the Spiral/N-pillar interface. The interaction with ABL1 is in aa 1373-1382. CLK2, a regulator of ATM, stability binds to aa 830-1290 and aa 2680-3056.
ATM homodimer: The FATC, the LBE (aa 2791-2829), the activation loop (aa 2888-2910), and the PIKK regulatory domain form a compact arrangement that has been referred to as the FLAP. It joins the TRD3 helices (aa 2378-2476), referred to as the FLAP binding element (FLAP-BE)). FLAP and FLAP-BE can form either an open dimer with a limited intermolecular interface or a tightly packed closed dimer with a larger interface. The active site of the open dimer is compatible with substrate binding, whereas the PIKK regulatory domain blocks the active site in the closed dimer (Baretic et al., 2017).
 
  Figure 2: ATM gene and protein
Expression ATM is expressed in all tissues.
 
  Figure 3: ATM electron microscopy structure Images are taken from PhosphoSitePlus and ModBase
Localisation Mostly in the nucleus throughout all stages of the cell cycle.
Function ATM is a homeostatic protein kinase with an extremely broad range of roles in various cellular circuits (Shiloh et al., 2013; Guleria et al., 2016; Shiloh, 2014; Cremona et al., 2014; Ambrose et al., 2013; Espach et al., 2015; Awasthi et al., 2016).
The PI3 kinase signature is a motif characteristic of a protein family of which ATM is a member - the PI-3 kinase-like protein kinases (PIKKs; Lovejoy et al., 2009; Baretić et al., 2014). This family also contains the MTOR protein, which regulates many signaling pathways in response to nutrient levels, growth factors and energy balance (Alayev et al., 2013; Cornu et al., 2013); the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), which is involved in the NHEJ pathway of and other genotoxic stress responses (Davis et al., 2014; Jette N et al., 2015), SMG1, which plays a key role in nonsense-mediated mRNA decay (Yamashita, 2013); and ATR, which responds to stalled replication forks and a variety of DNA lesions that lead to the formation of single-stranded DNA, including deeply resected DSBs (Errico et al., 2012; Maréchal et al., 2013; Awasthi et al., 2016). The redundancy, crosstalk and collaboration between the latter three PIKKs, which collectively respond to a broad spectrum of genotoxic stresses, are being extensively investigated (Lovejoy et al., 2009; Maréchal et al., 2013; Sirbu et al., 2013; Thompson, 2012; Gobbini et al., 2013; Chen et al., 2012).
It should be noted that in A-T patients, the two PIKKs that converse and cooperate with ATM in the response to genotoxic stress, ATR and DNA-PK, remain active. In view of the functional relationships between the three protein kinases, some of ATM's duties are probably carried out to a certain extent by ATR and/or DNA-PK, in A-T cells. On the other hand, the lack of a very versatile member of this trio may lead to some suboptimal responses of the other two, if they depend on the crosstalk with ATM. This interesting question is a subject of intensive research.
Homeostatic protein kinase involved in many cellular circuits. A primary role in the DNA damage response. Activated vigorously by DNA double-strand breaks and activates a broad network of responses. ATM initiates cell cycle checkpoints in response to double-strand DNA breaks by phosphorylating TP53, BRCA1, H2AX, ABL1, NFKBIA and CHEK1, as well as other targets; in certain types of tissues ATM inhibits radiation-induced, TP53-dependent apoptosis.
  • Double strand breaks. The most widely documented function of ATM, and the one associated with its most vigorous activation, is the mobilization of the complex signaling network that responds to DSBs in the DNA (Shiloh Y et al., 2013; Cremona CA et al., 2014; Awasthi P et al., 2016; Thompson LH, 2012; McKinnon PJ, 2012). DSBs are induced by exogenous DNA breaking agents or endogenous reactive oxygen species (Schieber M et al., 2014), and are an integral part of physiological processes including meiotic recombination (Borde V et al., 2013; Lange J et al., 2011) and the rearrangement of antigen receptor genes in the adaptive immune system (Alt FW et al., 2013). DSBs are repaired via nonhomologous end-joining (NHEJ), or homologous recombination repair (HRR; Shibata A et al., 2014; Chapman JR et al., 2012; Jasin M et al., 2013; Radhakrishnan SK et al., 2014). DSBs also activates the DDR, a vast signaling network that mobilizes special cell cycle checkpoints, extensively alters the cellular transcriptome, and changes the turnover, activity and function of numerous proteins that ultimately leads to modulation of numerous cellular circuits. This network is based on a core of dedicated DDR players and the ad-hoc recruitment of proteins from many other arenas of cellular metabolism, which typically undergo special, damage-induced post-translational modifications (PTMs; Shiloh Y et al., 2013; Sirbu BM et al., 2013; Thompson LH, 2012) (Goodarzi AA et al., 2013; Panier S et al., 2013; Polo SE et al., 2011).
    Once ATM mobilizes the vast DDR network in response to a DSB (McKinnon PJ, 2012; Shiloh Y et al., 2013; Bhatti S et al., 2011), its protein kinase activity is rapidly enhanced, and PTMs on the ATM molecule are induced, including several autophosphorylations and an acetylation (Shiloh Y et al., 2013; Bhatti S et al., 2011; Bakkenist CJ et al., 2003; Kozlov SV et al., 2006; Bensimon A et al., 2010; Sun Y et al., 2007; Kaidi A et al., 2013; Paull TT, 2015).
    ATM subsequently phosphorylates key players in various arms of the DSB response network (Shiloh Y et al., 2013; Bensimon A et al., 2010; Matsuoka S et al., 2007; Mu JJ et al., 2007; Bensimon A et al., 2011), including other protein kinases that in turn phosphorylate still other targets (Bensimon A et al., 2011).
  • Single-strand break repair and base excision repair. A broader, overarching role for ATM in maintaining genome stability was recently suggested in addition to mobilizing the DSB response (Shiloh Y, 2014). According to this conjecture, ATM supports other DNA repair pathways that respond to various genotoxic stresses, among them single-strand break repair (SSBR; Khoronenkova SV et al., 2015) and base excision repair (BER) - a cardinal pathway in dealing with the daily nuclear and mitochondrial DNA damage caused by endogenous agents (Wallace SS, 2014; Bauer NC et al., 2015).
    ATM's involvement in these processes is based on its ability to phosphorylate proteins that function in these pathways. In this way ATM also takes part also in resolving non-canonical DNA structures that arise in DNA metabolism, and in regulating other aspects of genome integrity such as nucleotide metabolism, the response to replication stress, and resolution of the occasional conflicts that arise between DNA damage and the transcription machinery. ATM is not critical for any of these processes in the same way it is for the DSB response, but rather contributes to their regulation (in most cases, their enhancement) when the need arises (Shiloh Y, 2014; Segal-Raz H et al., 2011; Zolner AE et al., 2011).
    This function of ATM may explain the moderate, variable sensitivity of ATM-deficient cells to a broad range of DNA damaging agents. Among them are UV radiation, alkylating agents, crosslinking agents, hydrogen peroxide, 4-Nitroquinoline 1-oxide, phorbol-12-myristate-13-acetate and topoisomerase 1 poisons (Yi M et al., 1990; Ward AJ et al., 1994; Hoar DI et al., 1976; Paterson MC et al., 1976; Smith PJ et al., 1980; Mirzayans R et al., 1989; Henderson EE et al., 1980; Scudiero DA, 1980; Jaspers NG et al., 1982; Teo IA et al., 1982; Barfknecht TR et al., 1982; Fedier A et al., 2003; Leonard JC et al., 2004; Lee JH et al., 2006; Zhang N et al., 1996; Smith PJ et al., 1989; Alagoz M et al., 2013; Katyal S et al., 2014; Speit G et al., 2000; Shiloh Y et al., 1985; Hannan MA et al., 2002).
    ATM-deficient cells also exhibit reduced efficiency in resolving TOP1 (Topoisomerase I) -DNA covalent intermediates (Alagoz M et al., 2013; Katyal S et al., 2014).
    This ongoing role of ATM is its routine function in the daily maintenance of genome stability, while its powerful role in the DSB response is reserved for when this harmful lesion interferes with the daily life of a cell. Thus, when ATM is missing, not only is there markedly reduced response to DSBs, the ongoing modulation of numerous pathways in response to occasional stresses becomes suboptimal. All of these lesions are part of the daily wear and tear on the genome that contributes to ageing.
    An additional role for ATM in genome dynamics was proposed following evidence that ATM is involved in shaping the epigenome in neurons by regulating the localization of the histone deacetylase 4 ( HDAC4; Li J et al., 2012; Herrup K et al., 2013; Herrup K, 2013), targeting the EZH2 component of the polycomb repressive complex 2 (Li J et al., 2013), and regulating the levels of 5-hydroxymethylcytosine in Purkinje cells (Jiang D et al., 2015).
  • Oxidative stress/Cellular homeostasis.
    Cytoplasmic fraction of ATM. ATM's role in cellular homeostasis is further expanded by its cytoplasmic fraction. Specifically, cytoplasmic ATM was found to be associated with peroxisomes (Watters D et al., 1999; Tripathi DN et al., 2016; Zhang J et al., 2015) and mitochondria (Valentin-Vega YA et al., 2012). In view of the evidence of increased oxidative stress in ATM-deficient cells, it has long been suspected that ATM senses and responds to oxidative stress (Gatei M et al., 2001; Rotman G et al., 1997; Rotman G et al., 1997; Barzilai A et al., 2002; Watters DJ, 2003; Takao N et al., 2000; Alexander A et al., 2010). This conjecture was validated by work from the Paull lab (Guo Z et al., 2010a), which identified an MRN-independent mode of ATM activation, differentiating it from DSB-induced activation, stimulated by reactive oxygen species (ROS) and leading to ATM oxidation (Paull TT, 2015; Guo Z et al., 2010a; Guo Z et al., 2010b; Lee JH et al., 2014). ATM was also found to be involved specifically in the protection against oxidative stress induced by oxidized low-density lipoprotein (Semlitsch M et al., 2011). It has thus assumed the role of a redox sensor (Ditch S et al., 2012; Tripathi DN et al., 2016; Krüger A et al., 2011). Recently, the first phospho-proteomic screen was carried out to identify substrates of ROS-activated ATM (Kozlov SV et al., 2016). An important arm of the ATM-mediated response to ROS extends to peroxisomes (Tripathi DN et al., 2016). Work from the Walker lab showed that ROS-mediated activation of peroxisomal ATM leads to ATM-mediated phosphorylation of LKB and subsequent activation of AMPK and TSC2, which dampens mTORC1-mediated signaling, eventually decreasing protein synthesis and enhancing autophagy (Alexander A et al., 2010; Tripathi DN et al., 2013; Zhang J et al., 2013; Alexander A et al., 2010; Alexander A et al., 2010). Further work from this lab (Zhang J et al., 2015) showed that ATM also phosphorylates the peroxisomal protein PEX5, flagging it for ubiquitylation and subsequent binding to the autophagy adapter, SQSTM1 (p62), in the process of autophagy-associated peroxisome degradation (pexophagy) - a critical process in peroxisome homeostasis (Till A et al., 2012).
    Mitochondrial fraction of ATM. Still another arm of the ATM-mediated response to oxidative stress operates in the mitochondrial fraction of ATM. ATM is thus emerging also as a regulator of mitochondrial homeostasis. Evidence is accumulating of its involvement in mitochondrial function, mitophagy, and the integrity of mitochondrial DNA (Valentin-Vega YA et al., 2012; Ambrose M et al., 2007; Eaton JS et al., 2007; Fu X et al., 2008; Valentin-Vega YA et al., 2012; D'Souza AD et al., 2013; Sharma NK et al., 2014) and further work is needed to identify its substrates in mitochondria and the mechanistic aspects of its action in this arena.
  • Links between ATM and the SASP (senescence-associated secretory phenotype). Several laboratories recently described direct links between ATM and the SASP - a cardinal feature of cell senescence. Work from the Gamble lab (Chen H et al., 2015) showed that the histone variant macroH2A.1 is required for full transcriptional activation of SASP-promoting genes, driving a positive feedback loop that enhances cell senescence. This response is countered by a negative feedback loop that involves ATM activation by endoplasmic reticulum stress, elevated ROS levels or DNA damage. ATM's activity is required for the removal of macroH2A.1 from sites of SASP genes, thus leading to SASP gene repression. The Elledge lab identified a major SASP activator - the transcription factor GATA4, whose stabilization drives this process (Kang C et al., 2015). Importantly, the activation of this pathway was dependent on both ATM and ATR, as was senescence-associated activation of TP53 and CDKN2A (p16INK4a). On the other hand, the Zhang lab (Aird KM et al., 2015) recently showed that when cell senescence is induced by replication stress (e.g., following nucleotide deficiency), ATM inactivation allows the cell to bypass senescence by shifting cellular metabolism: upon ATM loss, dNTP levels rise due to up-regulation of the pentose phosphate pathway, whose key regulator, glucose-6-phosphate dehydrogenase ( G6PD) is under functional regulation by ATM (Aird KM et al., 2015; Cosentino C et al., 2011).
  • Insulin response and lipoprotein metabolism. Other metabolic arenas in which ATM involvement is gaining attention are insulin response and lipoprotein metabolism, clinically represented by the metabolic syndrome. This role of ATM in cellular physiology was recently thoroughly and convincingly reviewed (Espach Y et al., 2015). Briefly, ATM was found to participate in several signaling pathways mediated by insulin (Yang DQ et al., 2000; Miles PD et al., 2007; Viniegra JG et al., 2005; Halaby MJ et al., 2008; Jeong I et al., 2010); and heterozygosity for Atm null allele in ApoE-deficient mice was found to aggravate their metabolic syndrome (Wu D et al., 2005; Schneider JG et al., 2006; Mercer JR et al., 2010), an effect that was partly relieved by the mitochondria-targeted antioxidant MitQ (Mercer JR et al., 2012.
  • IGF1 receptor. Another pathway by which ATM may impact on cellular senescence is the dependence of IGF1R (IGF-1 receptor) expression on ATM (Peretz S et al., 2001; Goetz EM et al., 2011; Ching JK et al., 2013); the mechanism remains to be elucidated, but ATM impacts on IGF-1-mediated pathways, including those that affect cellular senescence (Luo X et al., 2014).
  • Beta-adrenergic receptor. Another series of observations assigned ATM a protective role in cardiac myocyte apoptosis stimulated by β-adrenergic receptor and myocardial remodeling. Loss of Atm in mice induced myocardial fibrosis and myocyte hypertrophy and interfered with cardiac remodeling following myocardial infarction (Foster CR et al., 2011; Foster CR et al., 2012; Foster CR et al., 2013; Daniel LL et al., 2014). The mechanistic aspects of these effects are still unclear, but ATM's apparent involvement in myocardial homeostasis might be relevant to the observation of elevated arteriosclerosis in A-T carriers (Swift M et al., 1983; Su Y et al., 2000).
  • Homology Phosphatidylinositol 3-kinase (PI3K)-like proteins, most closely related to ATR and the DNA-PK catalytic subunit.

    Mutations

    Note The cellular phenotype of A-T represents genome instability, deficient DNA damage response (DDR), and elevated oxidative stress, in addition to a premature senescence component (Shiloh et al., 1982).
    Germinal Various types of mutations have been described, dispersed throughout the gene, and therefore most patients are compound heterozygotes; most mutations appear to inactivate the ATM protein by truncation, large deletions, or annulation of initiation or termination, although missense mutations have been described in the PI3 kinase domain and the leucine zipper motif.
    Patients with the severe form of A-T are homozygous or compound heterozygous for null ATM alleles. The corresponding mutations usually lead to truncation of the ATM protein and subsequently to its loss due to instability of the truncated derivatives; a smaller portion of the mutations create amino acid substitutions that abolish ATM's catalytic activity (Taylor et al., 2015; Gilad et al., 1996; Sandoval et al., 1999; Barone et al., 2009) (see also http://chromium.liacs.nl/LOVD2/home.php?select_db=ATM).
    Careful inspection of the neurological symptoms of A-T patients reveals variability in their age of onset and rate of progression among patients with different combinations of null ATM alleles (Taylor et al., 2015; Crawford et al., 2000; Alterman et al., 2007). Thus, despite the identical outcome in terms of ATM function, additional genes may affect the most cardinal symptom of A-T. Other, milder types of ATM mutations further extend this variability, and account for forms of the disease with extremely variable severity and age of onset of symptoms. The corresponding ATM genotypes are combinations of hypomorphic alleles or combinations of null and hypomorphic ones. Many of the latter are leaky splicing mutations and others are missense mutations, eventually yielding low amounts of active ATM (Taylor et al., 2015; Alterman et al., 2007; Soresina et al., 2008; Verhagen et al., 2009; Silvestri et al., 2010; Saunders-Pullman et al., 2012; Verhagen et al., 2012; Worth et al., 2013; Claes et al., 2013; Méneret et al., 2014; Nakamura et al., 2014; Gilad et al., 1998).
    Somatic B A variety of missense somatic, biallelic mutations were identified in hematologic malignancies, most notably mantle cell lymphoma and T-prolymphocytic leukaemia.
    Missense mutations outside of the PI3 kinase and leucine zipper domains have been described among breast cancer patients, although these mutations have not been found in A-T patients. Whether these mutations contribute to breast cancer though not to ataxia-telangiectasia remains controversial.

    Implicated in

    Note Germline mutations: Ataxia telangiectasia syndrome is associated with greater than 100-fold increased risk of leukemias and lymphomas
    From a total of 296 consecutive genetically confirmed A-T patients, 66 patients who developed a malignant tumor; 47 lymphoid tumors and 19 non-lymphoid tumors were diagnosed. The development of childhood tumors below 16yrs (33 lymphoid and 3 brain) in A-T patients is associated almost exclusively with the absence of ATM kinase activity. After the age of 16yrs, there were 11 lymphoid malignancies, and 13 other tumors (including 7 breast cancers) (Reiman et al. 2011).
    Two-hundred seventy-nine patients with AT were enrolled in a registry. Sixty-nine patients developed 70 malignancies. Cancer types were mainly lymphoid (4 T-cell ALLs (acute lymphoblastic leukemia), 2 B-cell ALLs, 12 Hodgkin lymphomas, 26 B-cell NHL (non-Hodgkin lymphoma), 4 T-cell NHL, 3 T-PLL (T prolymphocytic leukemia), and carcinomas (3 breast, 2 gastric, 2 liver). The median age at diagnosis of malignancy of any type was 12.5 years (10yrs for most lymphoid diseases, 24yrs for T-PLL, and 31yrs for carcinomas) (Suarez F et al. 2015).
    Somatic mutations: According to COSMIC, somatic mutations in ATM are the following: missense substitution (57%), nonsense substitution (12%), synonymous substitution (6%), frameshift deletion (6%), frameshift insertion (2%), inframe deletion (1%), complex mutation (0.2%), inframe insertion (0.02%). They are found in the following cancers: meningioma 12%; endometrium 12% (undifferentiated-dedifferentiated carcinoma 20%, endometrioid carcinoma 15%, clear cell carcinoma 11%); prostate 12%; bladder 10%; colorectal adenocarcinoma 9%; liver cancers 5% (combined hepatocellular-cholangiocarcinoma 10%, hepatocellular carcinoma 4%); stomach adenocarcinoma 7%; haematopoietic and lymphoid 7% (T cell prolymphocytic leukemia 45%, mantle cell lymphoma 20-45%, chronic lymphocytic leukaemia 12%, diffuse large B cell lymphoma 6-9%, multiple myeloma 5%, follicular lymphoma 4%, adult T cell lymphoma-leukemia 4%, ALL 3%, AML (acute myeloid leukemias) 2%, Burkitt lymphoma 1%); lung 7% (adenocarcinoma 7%, squamous cell carcinoma 6%, small cell carcinoma 4%); biliary tract 6%; ovary 5% (mixed adenosquamous carcinoma 21%, serous carcinoma 4%); pancreas 5%; oesophagus 4% ( adenocarcinoma 9%, squamous cell carcinoma 3%); breast 4%; soft tissue 3% (alveolar rhabdomyosarcoma 5%, embryonal rhabdomyosarcoma 3%, liposarcoma 3%), thyroid 3% ( anaplastic carcinoma 5%, papillary carcinoma 2%, medullary carcinoma 2%, follicular carcinoma 2%); kidney 3% (clear cell renal cell carcinoma 3%, papillary renal cell carcinoma 3%); cervix squamous cell carcinoma 3%; testis 2%; bone 2%; ( Ewing sarcoma_peripheral primitive neuroectodermal tumor 1%); central nervous system 2% (astrocytoma Grade III or IV 2%).
    PhosphositePlus give the following data: bladder: 12%; endometrial: 12%; colorectal 11%; stomach 10%; lung adenocarcinoma 9%; lung (squamous cell) 5%; prostate 4%; kidney (clear cell or chromophobe) 3%; head/neck 3%; breast 2%; glioblastoma 1%; ovary 1%; thyroid 1%.
    Translocations: In contrast, translocations/hybrid genes and fusion proteins involving ATM are extremely rarely found:
    in lung adenocarcinoma (Yoshihara et al, 2015) PMID 25500544
    ATM (11q22.3) / ATM (11q22.3) in T-cell prolymphocytic leukemia (Bradshaw et al., 2002) and in breast invasive carcinoma.
    DDX10 (11q22.3) / ATM (11q22.3) in a cell line (Klijn et al., 2015).
    CUL5 (11q22.3) / ATM (11q22.3) in a cell line (Klijn et al., 2015).
    and, according to ChimerDB 3.0 and/or ChiTaRS databases: ITGB8 (7p21.1) / LOC440600 (1p13.3) in uterine corpus endometrial carcinoma, ATP6V1C2 (2p25.1) / ATM (11q22.3), CUX1 (7q22.1) / ATM (11q22.3), ASPH (8q12.3) / ATM (11q22.3) in diseases not specified.
      
    Entity Ataxia telangiectasia
    Note Ataxia telangiectasia is a prototype genome instability syndrome (Perlman SL et al., 2012; Lavin MF, 2008; Crawford TO, 1998; Chun HH et al., 2004; Taylor AM et al., 1982; Taylor AM et al., 2015; Taylor AM, 1978; Butterworth SV et al., 1986; Kennaugh AA et al., 1986).
    Disease Ataxia telangiectasia is a progressive cerebellar degenerative disease with telangiectasia, immunodeficiency, premature aging, cancer risk, radiosensitivity, and chromosomal instability.
    Prognosis Prognosis is poor: median age at death: 17 years; survival rarely exceeds 30 years, though survival is increasing with improved medical care.
    Cytogenetics Spontaneous chromatid/chromosome breaks; non clonal stable chromosome rearrangements involving immunoglobulin superfamilly genes e.g. inv(7)(p14q35); clonal rearrangements.
      
      
    Entity Colorectal adenocarcinoma
    Note R337C/H is a hotspot mutation prominent in colorectal cancer. Methylation data in TCGA datasets revealed significant negative correlations between ATM promoter methylation and ATM gene expression in colon adenocarcinoma. ATM promoter methylation may play a role in the regulation of ATM gene expression in these cancer types (Jette et al., 2020).
    Somatic mutations: In a study of 148 colon adenocarcinoma, eight of the genes evaluated were mutated in greater than 20% of the 148 carcinomas, the genes carrying the highest somatic mutation were: APC, 68%; TP53, 47%; ATM, 21% (equally found in microsatellite stable and in microsatellite instable tumors). No ATM mutation was found in adenoma samples (Wolff et al., 2018). However, ATM mutations were found in colon adenomas in another study (Lee et al., 2017). In a series of 908 stage II/III colorectal cancers, reduced ATM expression was an independent marker of poor disease-free survival (Beggs et al., 2012). ATM deletions were found in 7 of 13 gastrointestinal stromal tumors (Ul-Hassan et al., 2009).
    Expression: 5 adenomas and 10 adenocarcinoma, paired with normal tissues were analyzed. Changes in DNA methylation have been shown to be associated with the progression of colorectal cancer. Methylation changes in the progression from normal mucosa to adenoma and to carcinoma. The highest-rated gene in term of hypermethylation, when comparing carcinomas versus adenomas was ATM. The promoter region of ATM was significantly methylated in the transition from adenoma to carcinoma; however, this does not correlate with expression of ATM. Not all gene promoter regions control expression of that gene and it is possible that control of expression of ATM is via another mechanism (Beggs et al., 2013).
    Cancer cell lines: ATM deficiency in colon cancer cell lines inhibits cancer cell proliferation, migration, and invasion, and results in cell cycle arrest and senescence via CHEK1/TP53/CD44 signaling activation (Liu et al., 2017).
    Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome, is due to an inherited mutation in one of five DNA mismatch repair genes EPCAM, MLH1, MSH2, MSH6, PMS2). ATM 1853N plays a notable part in changing the penetrance of germ-line mutations: HNPCC patients with ATM 1853N variant have an 8 times higher risk of forming a HNPCC-related cancer. Complete loss of ATM expression resulted in a propensity of worse survival, with increase in mortality rate (Sriramulu et al., 2019).
    Prognosis Poly-ADP-Ribose Polymerase ( PARP1) inhibitors have shown to increase the activity of DNA damaging chemotherapeutics used in the treatment of colorectal cancer cell lines, as well as patient-derived 3D spheroids, harboring pathogenic ATM mutations are significantly vulnerable to PARP1 inhibitors/chemotherapy combination (Vitiello et al., 2021).
      
    Entity Gastric cancer
    Note ATM is frequently altered or deleted in gastric cancer.
    Germline mutations: A total of 282 patients with gastric adenocarcinoma (182 males and 100 females) were enrolled in a study. The most recurrent germline mutation was a mutation in ATM (1%) (Ji et al., 2020). A large study involving more than 600,000 cancer patients found that 0.7% patients had an ATM pathogenic variant. A higher risk for gastric cancer was estimated (OR (odds ratio), 2.97; 95% CI, 1.66-5.31) (Hall et al., 2021). In a case-control investigation of 345 gastric adenocarcinoma patients and 467 controls, the ATM rs189037 G>A polymorphism was associated with a significantly higher risk of gastric cancer, and patients with this polymorphism had lower overall survival (Tao et al., 2020).
    Somatic mutations: A panel of 543 cancer-associated genes was used to analyze genomic profiles in a cohort of 484 patients with gastric cancer. Fifty-one of the 484 (10.5%) patients carried at least one somatic mutation in an homologous recombination (HR) gene; ATM (16/484, 3.3%) was among the most frequently mutated HR genes (Fan et al., 2020). Two independent cohorts, a training set (n=524) and a validation set (n=394), of gastric cancer patients were enrolled. ATM, CHEK2, and TP53 expressions were examined. Somatic ATM loss, CHEK2 loss, and TP53 positivity were observed in 22%, 14%, and 36% of the training set, and in 17%, 12%, and 36% of the validation set. Also, patients with non-aberrant expressional levels of all 3 DNA damage response-related proteins had a more favorable outcome than others (Lee et al., 2014).
    Expression: Decreased expression and phosphorylation of ATM at serine 1981 ("S1981") were consistently found in tumors. Low level of phosphorylated ATM was significantly correlated with poor differentiation, lymph node metastasis and poor 5-year survival (Kang B et al., 2008). ATM is a target of "miR-181a" ( MIR181A1 (1q32.1) or MIR181A2 (9q33.3)). There is an inverse correlation between miR-181a and ATM protein expression in gastric cancer. Over-expression of miR-181a might be involved in development of gastric cancer by promoting proliferation and inhibiting apoptosis probably through directly targeting ATM (Zhang et al., 2014).
    Prognosis 123 randomly assigned patients received treatment (PARP1 inhibitor/taxane vs placebo/taxane). The prevalence of low ATM expression in patients was 14%. PARP1 inhibitor/taxane is active in the treatment of patients with metastatic gastric cancer, with a greater overall survival benefit in ATM low patients (Bau et al., 2010).
      
      
    Entity Salivary gland basal cell adenoma
    Note A missense mutation in the ATM gene (c.2572T>C, p.F858L) was seen in a basal cell adenoma with an allele frequency of 53 %, raising the possibility of a germline mutation (Wilson et al., 2016).
    48 samples of adenoid cystic carcinoma were studied. Low expression of ATM in cancer cells was significantly correlated with poor survival, while Low ATM expression in stromal fibroblasts was not significantly correlated to patient survival (Bazarsad et al., 2018)
      
      
    Entity hepatocellular carcinoma and cholangiocarcinoma
    Note Germline/somatic mutations: A comprehensive genomic profiling identified 3,765 gene aberrations in 760 in gallbladder cancers (but no germline testing was performed). Each tumor harbored at least 1 gene aberration, with an average of 5 gene aberration per tumor About 15 genes were implicated, from TP53, was the most recurrently found, in 61% of tumors, CDKN2A in 29%, … to ATM in 6%. (Abdel-Wahab et al., 2020). 131 patients with biliary tract cancers ( intrahepatic cholangiocarcinoma (64%), gallbladder adenocarcinoma (17%), extrahepatic cholangiocarcinoma (16%) and otherwise unspecified (4%)) were studied, 15 oncogenic somatic mutations in BAP1 or ATM were found. There was no case of ATM germline mutation (Maynard et al., 2020). 357 patients with liver cancer (214 with hepatocellular carcinoma, 122 with intrahepatic cholangiocarcinoma, and 21 with mixed hepatocellular-cholangiocarcinoma) were studied. 26% patients had at least one DNA damage repair (DDR) gene mutation, 15 of whom carried germline mutations (in BRCA2, BRCA1, ATM, PMS2 ….). The most commonly DDR genes with somatic mutations were ATM (5%) and BRCA1/2 (5%). 9 % of patients with intrahepatic cholangiocarcinoma had BRCA1/2 somatic mutations, and 6% of patients with hepatocellular carcinoma had ATM somatic mutations (Lin et al., 2019).
    Expression: Fifty pairs of hepatocellular carcinoma specimens and corresponding adjacent liver tissues were collected. The methylation frequency of the ATM promoter was significantly higher in hepatocellular carcinoma tissues than in normal liver tissues. Methylated ATM was correlated with lower ATM expression. Methylation of the ATM promoter was significantly associated with better outcome in patients with locally advanced hepatocellular carcinoma who initially received radiotherapy (Yan et al., 2020).
      
      
    Entity pancreatic cancers
    Note Pancreatic ductal adenocarcinoma: 1 to 4% of patients with pancreatic ductal adenocarcinoma with or without a family history of pancreatic cancer have a pathogenic germline ATM variant, and 2 to 18% of pancreatic ductal adenocarcinoma samples have somatic ATM alterations, either mutations, or loss of heterozygosity. Patients with loss of ATM expression and normal TP53 expression had decreased overall survival compared to patients with loss of ATM expression and abnormal TP53 expression, indicating that ATM expression may be an important prognostic factor for survival in patients with pancreatic cancer (review in Nanda and Roberts 2020). A large study involving more than 600,000 cancer patients with various cancers found that 0.7% patients had a germline ATM pathogenic variant. A higher risk for pancreatic cancer was found (OR= 4.2) (Hall et al., 2021).
    Hereditary pancreatic cancer: 5%-10% of pancreatic ductal adenocarcinoma are hereditary pancreatic cancers. A subset of familial pancreatic cancer have germline mutations in DNA repair genes BRCA2, ATM, or PALB2 (review in Bakker and de Winter. 2012; Rustgi 2014). In a series of 166 familial pancreatic cancer probands, 2.4% carried germline heterozygous ATM mutations. In one patient, the tumor analysis showed the second allele of ATM to be mutated, suggesting that the ATM loss in this patient was driven by the classic two-hit model (Roberts et al., 2012). 638 patients with familial pancreatic cancers were selected and whole genome sequencing was performed. The highest ranked gene was ATM with 19 heterozygous premature truncating variants, followed by TET2 (9 variants), DNMT3A (7), POLN and POLQ (6 each) etc … (Roberts et al., 2016). ATM loss was observed in 50 of 396 (13%) pancreatic ductal adenocarcinomas tumors, and more often in patients with a family history of pancreatic cancer (25%) than in those without (11%). ATM loss was associated with a significantly poorer outcome in patients with normal TP53 expression (Kim et al., 2014). A classification of high-to-moderate risk of pancreatic cancer in familial pancreatic cancer families according to germ-line mutation was defined: while cases with a mutation in CDKN2A, BRCA2, or PALB2 were high risk mutations, ATM, BRCA1 and mismatch genes were classified moderate risk mutation genes (Llach et al., 2020). 549 patients diagnosed with pancreatic ductal adenocarcinoma were included in another study. Germline pathogenic variants were identified in 16 genes, including ATM (11 cases, 2%). No patient with CHEK2 or ATM pathogenic variants responded to treatment with PARP1 inhibitor (Fountzilas et al., 2021). Of 708 patients with pancreatic cancer, eleven pathogenic germline mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53 (Grant et al., 2015). 96 patients, in another study, were tested. Fourteen pathogenic mutations were identified: four in ATM, two in BRCA2, CHEK2, and MSH6, and one in BARD1, BRCA1, FANCM, and NBN. (Hu et al., 2016).
    E2F1 can induce the long noncoding RNA CDKN2B-AS1 expression through the ATM/E2F1 signaling pathway. CDKN2B-AS1 overexpression promotes epithelial to mesenchymal transition in pancreatic cancer cells. CDKN2B-AS1 can repress the ATM/E2F1 signaling pathway by negatively regulating the expression of CDKN2A and CDKN2B (Chen et al., 2017).
    ATM deficiency accelerates metastatic murine pancreatic ductal adenocarcinoma formation, leads to persistent DNA damage, increases chromosomal instability, and also renders murine pancreatic tumors highly sensitive to radiation (Drosos et al., 2017).
    ATM expression was knocked down using shRNA in two cell lines. ATM-deficient pancreatic cancer cells were found to be more sensitive to radiation, but not to chemotherapeutic agents than wild-type pancreatic cancer cells (Ayars et al., 2017).
    107 pancreatic neuroendocrine tumors specimens were investigated. High expression of ATM and CCNB1 (cyclin B1) was related to well-differentiated endocrine tumors. The high ATM expression group had a significantly lower recurrence rate (Shin et al., 2012)
    Prognosis Therapeutic implications of ATM alterations: clinical trials that target ATM-deficient tumors especially with PARP1 inhibitors are reviewed in Armstrong et al., 2019.
      
      
    Entity Thyroid cancers
    Note Papillary thyroid carcinoma: 522 patients with papillary thyroid carcinoma and 885 control cases were studied; the CG/GG genotypes of rs1800057 were significantly associated with an increased risk of papillary thyroid carcinoma, and the AG/GG genotypes of rs189037 was inversely associated with papillary thyroid carcinoma risk. (Xu et al., 2012). A possible association between ATM rs189037 G>A polymorphisms and metastasis of papillary thyroid cancers was detected in female patients, but not in male patients (Gu et al., 2014). Of note is that ATM rs189037 G>A genetic polymorphism has also been proposed to contribute in an increased risk of head and neck and lung cancer (Bhowmik et al., 2015). In a study on 437 papillary thyroid carcinoma and 184 cancer-free controls, 3 ATM SNPs (rs373759, rs664143, and rs4585) were in strong linkage disequilibrium. When the three haplotypes (C-A-G), (T-G-T), and (C-G-T) of these three ATM SNP sites were analyzed, ATM haplotype (C-G-T) +/- was associated with a lower risk of papillary thyroid carcinoma than ATM haplotype (C-G-T) -/- (Song et al., 2014).
    Familial non-medullary thyroid cancer: Consistent ATM variants (ATM p.P1054R-rs1800057- and rs149711770) were described in families with familial non-medullary thyroid cancer (Miasaki et al., 2020). 277 cancer predisposition genes were tested in 17 families with familial non-medullary thyroid cancer. One frameshift variant and five missense variants. An ATM variant was identified in 3 instances in 2 families (Wang et al., 2019).
      
      
    Entity Pheochromocytoma
    Note Seven of thirty-eight patients with pheochromocytoma had heritable mutations including RET (n=3), VHL (2), SDHB (1), and ATM and PDGFRA (1 each) (Xiong MJ, Osunkoya 2020).
      
      
    Entity Breast cancer
    Note Ataxia-telangiectasia: Early reports were somewhat contradictory. In 161 families affected by ataxia-telangiectasia, ATM mutation heterozygotes were found to have double fold more breast cancer chance comparable to the normal population. This likelihood was upgraded 5-fold in women below age of 50 (Swift et al., 1991), but another study concluded that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer (FitzGerald et al., 1997). Of more than 1,500 mutations reported from A-T patients listed in the ATM Mutation Database (www.lovd.nl/ATM) greater than 80% are predicted to truncate the protein with no obvious clustering in specific regions of the gene (Bernstein Wecare Study Collaborative Group 2017). 443 BRCA1/2 negative familial breast cancer cases and 521 controls were studied. ATM mutations known to cause ataxia-telangiectasia were found: 12 in familial breast cancer cases and 2 in controls. 37 nonsynonymous missense variants were identified, 12 of which were present in both cases and controls, 15 were present exclusively in cases and 10 were present exclusively in controls. There was no difference in frequency between cases and controls for classical missense variants S49C, F858L, P1054R, L1420F and D1853N. The relative risk of breast cancer associated with ATM deleterious mutations was estimated to be 2.4 (Ahmed and Rahman 2006). From a total of 296 consecutive genetically confirmed A-T patients, 66 patients who developed a malignant tumor; 47 lymphoid tumors and 19 non-lymphoid tumors were diagnosed. After the age of 16yrs, there were 11 lymphoid malignancies, and 13 other tumors, including 7 breast cancers (Reiman A et al. 2011). Germline mutations are found in up to 3% of hereditary breast and ovarian cancer families. In a review of breast tumors of 21 ataxia-telangiectasia family cases, ATM-associated tumors are near-tetraploid in 70% of cases and show loss of heterozygosity (67%) at the ATM locus. Tumors arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability. ATM-associated tumors are distinct from BRCA1-associated tumors in terms of morphological characteristics and genomic alterations, and they are also distinguishable from sporadic breast tumors. 97% of ATM-associated tumors were ER+. The luminal B (ER+, PR+/-, ERBB2 (HER2)- and Ki-67 ≥20%) subtype (46%) was over-represented among tumors developed by A-T participants (Renault AL et al., 2018).
    Other germline mutations: In a meta-analysis, Byrnes et al., 2008 concluded that germline mutations in ATM, BRIP1, PALB2 and CHEK2, that are known to interact with BRCA1 and BRCA2, may be associated with a high risk of breast cancer for a subset of women. Coding regions ATM, CHEK2, PALB2 and XRCC2 were analyzed in 13,087 breast cancer cases and 5,488 controls. 1,273 variants were identified in the four genes: 785 in ATM, 165 in CHEK2, 255 in PALB2 and 68 in XRCC2. PALB2 truncating variants were associated with the highest breast cancer risk, with an estimated OR=4.7; the risk for ATM and CHEK2 truncating variants were OR=3.3 and OR=3.1 respectively. There was no association between XRCC2 truncated variants and breast cancer risk. Truncating ATM variants were more common in breast cancer cases with a family history of breast cancer, and with ER+ cases. Missense variants in ATM, CHEK2 and PALB2 did not seem to contribute to breast cancer risk (Decker et al., 2017). A large study involving more than 600,000 cancer patients with various cancers found that 0.7% patients had an ATM pathogenic variant. In particular, 7271T>G was associated with higher invasive ductal breast cancer risk than other missense and truncating ATM pathogenic variants. Low-to-moderate risks were seen for ductal carcinoma in situ, male breast cancer, and ovarian cancer. 7271T>G is associated with high risk for breast cancer, with a 3- to 4-fold risk increase. Carriers are eligible for increased breast and pancreatic cancer screening for prevention and/or early detection (Hall et al., 2021). A meta-analysis was performed concerning the association between ATM variants and the risk of breast cancer. The OR of this association was estimated at 1.7- 2.3. V2424G variant (c.7271T>G) was the most associated with breast cancer incidence (Moslemi et al., 2021)
    Expression: ATG4C is responsible for autophagic activity. Downregulation of ATM expression induces a decrease in the autophagic flux. ATM expression regulates ATG4C levels. Positive correlation between ATM and ATG4C expression was found in all subtypes of breast cancer human samples (511 breast cancer samples from TCGA), except for the basal like subtype (the 4 subtypes are: 2 estrogen receptor (ER)-positive (estrogen receptors ESR1 and ESR2)subtypes, with either low (luminal A) or high (luminal B) expression of proliferation-related genes, a subtype enriched for ERBB2 (HER2)-amplified tumors, and the " basal " or triple-negative subtype (ER-, PR-, ERBB2-) (Antonelli et al., 2017). In a series of n=1106 samples (with ER (estrogen receptor) status (n=1055) positive 79%/negative 21%, PGR (progesterone receptor ) status (n=1052) positive 67%/negative 33%, ERBB2 (n=1066) positive 13%/negative 87%, ER/PR/ERBB2 (n=1013) Positive for at least one 86%/triple negative 14%, immunohistochemical TP53 positive 21%/negative 79%), ATM protein expression was reduced more frequently among BRCA1 (33%) and BRCA2 (30%) tumors than in non-BRCA1/2 tumors (11%). In a series of 1013 non-BRCA1/2 cases, ATM was more commonly deficient (20%) and TP53 was overabundant (47%). The non-BRCA1/2 tumors with reduced ATM expression were more often ER-, PR- and were of higher grade (Tommiska J et al., 2008).
      
      
    Entity Ovarian carcinoma and Fallopian tube carcinoma
    Note High grade serous ovarian cancer is the most common epithelial ovarian cancer subtype.
    Germline mutations: Pathogenic germline BRCA1, BRCA2, and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma, classified as high-grade serous carcinoma. Pathogenic variants of 11 genes were identified in 41 (18%) women: 19 (8%; BRCA1), 8 (4%; BRCA2), 6 (3%; mismatch repair genes), 3 (1%; RAD51D), 2 (1%; ATM) (Hirasawa et al., 2017). Germline mutations in 174 cases of extrauterine high-grade serous carcinomas (located in the fallopian tube, ovary, or peritoneum) were studied. 79% of tumors were high-grade serous ovarian carcinoma (n=138), and the most common mutations in high-grade serous carcinomas were TP53 (94%), BRCA1 (25%), BRCA2 (11%), and ATM (7%). ATM mutations were found in high-grade serous carcinoma (6 of 138 cases), endometrioid carcinoma (2 of 12 cases), and clear cell carcinoma (1 of 10 cases). (Ritterhouse et al., 2016). Germline pathogenic variants: a large study involving more than 600,000 cancer patients with various cancers found that 0.7% patients had an ATM pathogenic variant. Low-to-moderate risks were seen for ovarian cancer (OR= 1.57; 95% CI, 1.35-1.83) (Hall et al., 2021).
    Germline/somatic mutations: 390 ovarian carcinomas were screened. Thirty-one percent of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 homologous recombination genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, ABRAXAS1, MRE11, NBN, PALB2, RAD51C, and RAD51D. Germline and somatic mutations in ATM were present respectively in 0 (0%) and 2 (6%) of cases (Pennington et al. 2014).
    Somatic mutations: Among 207 ovarian cancer patients, ATM somatic mutation was more frequently detected in clear cell carcinomas (9%) and endometrioid carcinomas patients (18%) than in high-grade serous carcinomas patients (4%) (Sugino et al., 2019).
    Expression: Wildtype ATM is upregulated in high grade serous ovarian cancer patients compared to normal fallopian tube tissue, as indicated by increased S1981 autophosphorylation (Chen et al., 2020). Seventeen primary serous ovarian cancers were studied; a worse outcome was found in patients with low EZH2 and high-ATM-expressing tumors, compared with patients with low EZH2 and low-ATM-expressing tumors. In the group with low EZH2 expression, the median survival was higher in low-ATM than in high-ATM (20 months vs. 14 months (Naskou et al., 2020).
      
      
    Entity Uterine cancers
    Note One-hundred forty-one primary uterine cervical lesions and corresponding normal tissues were collected. In cervical intraepithelial neoplasia, comparable frequency of alterations (deletion/methylation) was seen in CADM1 (24%) and ATM (21%). In cervical carcinoma, higher alterations were seen in CADM1 (59%) and ATM (49%). In primary cervical carcinoma, high reduction in expression of CADM1, ATM, and PPP2R1B were found. Low expression and high alterations (55-59%) of ATM, CADM1 or CHEK1 was correlated with poor outcome (Mazumder Indra et al., 2011).
    Somatic mutations in ATM were found in 2 of 7 uterine leiomyosarcomas, 2 of 7 endometrial stromal sarcomas, and 1 of 5 uterine carcinosarcomas (da Costa et al,. 2021.). In another study, 5 mutations were found in 4 of 25 cases of leiomyosarcomas (Lee et al., 2017). ATM deletions were found in 16 of 20 leiomyosarcomas (Ul-Hassan et al., 2009).
      
      
    Entity Testicular germ-cell tumors
    Note Expression: Among testicular germ-cell tumors, high levels of S1981-phosphorylated ATM (pS-ATM) was observed especially in embryonal carcinomas, less in seminomas, rarely in teratomas or carcinoma in situ. However, it was lower in testicular germ-cell tumors than is known in carcinomas (Bartkova et al., 2005).
      
      
    Entity Prostate cancer
    Note Germline mutations: Hereditary factors: The proportion of all prostate cancers due to high-risk hereditary factors is about 8-12%. Germline mutations/alterations associated with elevated risk of prostate cancer were: BRCA1 1.8-3.8 fold increased relative risk; BRCA2 2.5-4.6 fold increased relative risk<55 years; CHEK2 1.9-3.3 fold increased overall risk; ATM 6.3 fold increased relative risk; mismatch genes 3.7 fold increased relative risk; HOXB13 3.4-8.6 fold increased relative risk (review in Heidegger et al., 2019). A study reported data from 3,607 men with a personal history of prostate cancer who underwent germline genetic testing. 620 (17 %) had positive germline variants. Variants as a percentage of men tested were as follows: BRCA2, 4.7%; CHEK2, 2.9%; MUTYH, 2.4%; ATM, 2%; etc… (Nicolosi et al., 2019). A large study involving more than 600,000 cancer patients with various cancers found that 0.7% patients had an ATM pathogenic germline variant. Higher risk for prostate cancer was found (OR= 2.58; 95% CI, 1.93-3.44) (Hall et al., 2021).
    Germline/somatic mutations: The incidence of BRCA1, BRCA2, ATM and CHEK2 mutations is higher in metastatic than in localized prostate cancer, as summarized by Sigorski et al., 2020: localized prostate cancer: BRCA2: <1% germline mutations / 3% somatic mutations; ATM: 1% germline / 4% somatic; BRCA1: <1% germline / 1% somatic; CHEK2: <1% germline / 0% somatic. Metastatic prostate cancer: BRCA2: 5% germline / 13% somatic; ATM: 2% germline / 7% somatic; BRCA1: <1% germline / <1% somatic; CHEK2: 2% germline / 3% somatic (Sigorski et al., 2020). Next-generation sequencing identified deletions and mutations in 50 patients with metastatic, castration-resistant prostate cancer. 21 patients had defects in DNA-repair genes in their tumor (BRCA2 in 9 cases, ATM in 6 (1 case with monoallelic germline mutation, 3 with monoallelic somatic mutations and 2 with germline mutation plus a somatic loss of heterozygocity, FANCA in 3 …etc). (Mateo et al., 2015). Samples were obtained from 45 patients and 182 cancer-associated genes were tested. Forty four per cent of cases had genomic alterations involving AR (androgen receptor) and 44% as well showed TMPRSS2 translocations, PTEN loss (found in 44%). TP53 mutation (40%); RB1 loss (28%); MYC gain (12%); BRCA2 loss (12%); ATM) mutations (8%); PIK3CA mutation (4%) (Beltran et al., 2013)
    Higher prevalence of aberrations in key DNA repair genes (homologous recombination genes BRCA2 and ATM, and mismatch repair genes) (23%), TP53 (53%), RB1 (21%), the PTEN/PI3K/AKT/MTOR pathway (49%), and AR (63%) in castration-resistant prostate cancers than in localized prostate cancer was confirmed (review in Mateo et al., 2017). Twelve per cent of the lethal prostate cancer cases presented potentially damaging protein-truncating variants in DNA repair genes, with CHEK2 (4%) and ATM (3%) being the genes most frequently altered (review in Brandao et al. 2020).
    Prognosis PARP1 inhibitors were found to be cytostatic, but not cytotoxic in ATM-deficient cancer cell lines and combination of PARP1 inhibitors with an ATR inhibitor is needed to induce cell death. Inhibition of ATR potentiates the effects PARP1 inhibition (Jette et al., 2020). Trials using PARP1 inhibitors are reviewed in Nizialek and Antonarakis 2020. The PARP1 inhibitors are now approved for prostate cancer. The combination of anti-hormonal therapy with DNA damage response inhibitors also has a potential enhanced efficacy (Wengner et al., 2020).
    Recommendations for prostate cancer early detection in carriers of high-risk mutations are the following: Begin screening at age 40 yrs: annual PSA dosage and digital rectal examination (men with a high PSA level are at higher risk for prostate cancer and aggressive prostate cancer.); If PSA is low and no other indication for biopsy, repeat screening in 12 months. If PSA is high, recheck PSA; if increased, consider biopsy (Cheng et al., 2019).
      
      
    Entity Bladder urothelial carcinoma
    Note Germline mutations: In a study of 1,038 patients with urothelial carcinoma, 24% harbored pathogenic germline variants. MLH1 and MSH2 were considered as urothelial carcinoma risk genes, and ATM (germline variant found in 13 of 827 cases) and BRCA2 (18 of 867 cases) were found as potential urothelial carcinoma predisposition genes (Nassar et al., 2020).
    Somatic mutations: Another study included 53 patients with urothelial carcinoma. 11% (6/53) of patients harbored ATM alterations in the tumor. ATM somatic alterations were associated with a significantly shorter overall survival (median survival 18 months vs 39 months) (Joshi et al., 2020). From an immunotherapy cohort (n = 210) and The Cancer Genome Atlas (TCGA)-Bladder cancer cohort, a series of analyses was performed to evaluate the prognostic value of ATM in bladder cancer immunotherapy. It was found that bladder cancer patients with ATM somatic mutation had greater benefit from Immune checkpoint inhibitors. ATM mutation significantly upregulated the number of DNA damage repair pathway gene mutations. ATM mutations resulted in increased bladder cancer sensitivity to 29 drugs, including an IGF1R inhibitor (Yi et al., 2020). Mutations of DNA repair genes, e.g. ATM/RB1, are frequently found in urothelial cancer and have been associated with better response to cisplatin-based chemotherapy. Overall, 31 out of 130 patients (24%) had somatic mutations in either ATM (19/130) or RB1 (ATM/RB1) genes in a TCGA dataset, while 18 out of 81 patients (22%) had mutations in hospitals dataset (with 12/81 ATM mutations). ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients (Yin et al., 2018).
      
      
    Entity Renal cell carcinomas
    Note Polymorphisms: (germline genetic variants): A total of 2,657 renal cell carcinoma (75% clear cell renal cell carcinoma, 8% papillary renal cell carcinoma, 17% other histology types) cases and 5,315 healthy controls were studied. Two single nucleotide polymorphisms (SNPs) that map to PIK3CG and ATM (rs611646:T, located in an intron of ATM) were significantly associated with renal cell carcinoma risk (Shu et al., 2018).
    Somatic mutations: 229 patients with metastatic clear cell renal cell carcinoma were included. The most frequently altered genes were CHEK2 (n=10; including three somatic and seven germline), ATM (n=8; all somatic), MSH6 (n=4; including three somatic and one germline) and MUTYH (n=4; all germline) (Ged et al., 2020). A total of 110 patients were selected in a study concerning the expression level of ATM. The expression of ATM in clear cell renal cell carcinoma is significantly lower than that in adjacent normal tissues. Further analysis found that the expression of ATM in the clear cell renal cell carcinoma tissues above grade II was lower than that of grade II or below. The survival time of the ATM low expression group was significantly shorter than that of the ATM high expression group (Ren et al., 2019).
      
      
    Entity Lung cancers
    Note Polymorphisms: ATM gene polymorphisms was evaluated in 616 lung cancer patients ( adenocarcinomas 27%, squamous cell carcinomas 39%, other non-small cell lung carcinoma 18%, small cell lung carcinoma 16%) and 616 controls. Subjects with the A allele at the site (IVS62+60G>A) have significantly higher risk of lung cancer than those with the G allele. Looking at the haplotypes of four ATM single nucleotide polymorphism sites (-4518A>G, IVS21-77C>T, IVS61-55T>C and IVS62+60G>A), the ATTA haplotype showed significantly increased risk of lung cancer (Kim JH et al., 2006). In a meta-analysis showed that the polymorphism rs189037 (G>A) was associated with the risk of lung cancer and breast cancer (Zhao et al., 2019). Moreover, the homozygote AA variant allele was found to be significantly related with the prognosis of lung cancer (Bhowmik et al., 2015). A comprehensive meta-analysis of 14 studies including 4,731 cases of small and non-small cell lung carcinomas and 5,142 controls was conducted to evaluate the association between ATM gene polymorphisms and both susceptibility to lung cancer. ATM rs189037, rs664677 and rs664143 gene polymorphisms are risk factors for lung cancer (Yan et al., 2017). ATM rs189037 (G>A), located at the 5'UTR of its promoter, is an important variant. Four eligible studies on lung carcinomas were included for meta-analysis; the histological type is however not defined in one of these studies. ATM rs189037 AA carriers had more risk of lung cancers than wild-type carriers. Specially, the association was more notable in non-smokers whereas no association of this variant with lung cancer risk was found in smokers (He et al., 2019). Homozygous variants rs227060 and rs170548) were associated with elevated risk for non-small cell lung carcinoma (Yang et al., 2007). In a case-control study, 852 "lung cancer" patients and 852 healthy controls, individuals carrying variant AA genotype of rs189037 had higher lung cancer risk (Liu et al. 2014). In a study of 720 non-small cell lung cancer patients (22% with squamous cell carcinoma, and 50% with adenocarcinomas) that have undergone radiation or chemo-radiation therapies: patients with rs664143 GA or AA genotype and patients with rs189037 AG/GG had poorer overall survival (Mou J et al., 2020).
    Smokers: Variant rs652311 may enhance the effect of smoking on lung cancer development and thereby increase lung cancer risk in smokers (Hsia et al., 2013). Polymorphisms rs189037, rs228597, rs228592, rs664677, rs609261, rs599558, rs609429, rs227062, and rs664982) were significantly associated with lung cancer among never-smokers, but not among smokers (Lo et al., 2010).See also the review by Xu et al., 2017).
    Somatic mutations: 188 primary lung adenocarcinomas were studied and 623 candidate genes were screened for somatic mutations. 1,013 non-synonymous somatic mutations were identified, including 14 ATM mutations in 13 tumors. Altogether, the genes most frequently mutated were: TP53 6.6%, KRAS 6.1%, STK11 3.4%, EGFR 3.4%, LRP1B 1.7%, NF1 1.6%, ATM 1.4%, APC 1.3%, EPHA3 1.1%, and PTPRD 1.0. A negative correlation between mutations in ATM and TP53 was detected, suggesting that mutations in ATM and TP53 may be independently sufficient for the loss of cell-cycle checkpoint control (Ding et al., 2008). In a vast multiple-cohort study, co-mutation of both ATM and TP53 has been shown to occur in 3-4% of non-small cell lung cancer. No significant differences in the TP53 and ATM comutation frequency was observed within the histologic subtypes (adenocarcinoma vs squamous cell carcinoma). ATM and TP53 comutation correlated with better response to immune checkpoint inhibitors therapy (Chen et al., 2019). Simple nucleotide variation (SNV), transcriptome profiling, copy number variation (CNV) and clinical data of patients were downloaded using TCGAbiolinks R package. EGFR, MGA, SMARCA4, ATM, RBM10, and KDM5C genes were found to be mutated only in lung adenocarcinoma, but not in lung squamous cell carcinoma. CDKN2A, PTEN, and HRAS genes are mutated only in lung squamous cell carcinoma samples. Both lung adenocarcinoma cases and lung squamous cell carcinoma cases have important gene alterations such as CDKN2B deletions (Zengin and Onal-Suzek, 2021).
    Expression: ATM is highly expressed in cisplatin-resistant non-small cell lung cancer cell lines. ATM enhances epithelial-to-mesenchymal transition (EMT) and metastatic potential via upregulation of CD274 (also called PD-L1), through JAK1,2/STAT3 pathway, in cisplatin-resistant non-small cell lung cancer cells, and inhibition of ATM suppresses tumor metastasis in xenograft mouse models (Shen et al. 2019). Methylation data in TCGA datasets revealed significant negative correlations between ATM promoter methylation and ATM gene expression in lung adenocarcinoma, and colon adenocarcinoma (Jette et al., 2020).
    Pulmonary neuroendocrine tumors: A total of 130 mutations were found in 29 genes and 49 patients (17 typical carcinoids, 17 atypical carcinoids, 19 large-cell neuroendocrine carcinomas, and 17 small-cell lung cancers. Four out of five ATM-mutated patients (1 large-cell neuroendocrine carcinoma) and 4 small-cell lung cancers, no carcinoid) showed an additional alteration in TP53, which was by far the most frequently altered gene (28 out of 130; 22%). Correlations between tumor type and grade for ATM and TP53-mutated patients were found. Both mutated genes were also associated with lymph node invasion and distant metastasis. The mutation frequency of APC and ATM in high-grade neuroendocrine lung cancer patients was associated with progression-free survival (Vollbrecht et al., 2015).
    Prognosis One hundred and sixty five non-small cell lung cancer samples (adenocarcinoma 54%, squamous cell carcinoma 29%, bronchoalveolar carcinoma 11%, other 6%) were analyzed for ATM expression. There was a moderate overexpression in tumor tissue and/but ATM loss was identified in 22% of patients. Compared to patients with a high malignant cell-specific ATM expression, patients with a low ATM expression had worse overall survival. Patients with low ATM expression treated with platin based perioperative treatment showed a strong trend toward improved disease free survival. This suggests that low ATM expression may be predictive of benefit from adjuvant platin based treatment (Petersen et al., 2017).
      
      
    Entity Brain tumors
    Note Polymorphisms: Five hundred and three meningioma cases, and 1,555 controls were analyzed in association with five polymorphisms in ATM (rs228599, rs3092992, rs664143, rs170548, rs3092993). Haplotypes were constructed using the HAPLOSTAT program. The haplotype analysis in ATM revealed an increased frequency of the 1-1-1-2-1 haplotype (34%) (Malmer et al., 2007). Pediatric brain tumors (93 pilocytic astrocytoma, 13 diffuse astrocytoma, 11 anaplastic astrocytoma, 20 "other gliomas", 19 ependymoma, 49 "other specified intracranial neoplasms" such as germinomas or dysembryoplastic neuroepithelial tumors, 26 ganglioglioma, 16 "unspecified intracranial neoplasm") were investigated. An increased risk of the non-astrocytoma subtypes (ependymomas …) was associated with the ATM single nucleotide polymorphisms rs170548 as well as polymorphisms in EGFR, EME1, and BICRA (Adel Fahmideh et al., 2016).
    Germline/somatic mutations: Genomic analysis of chordoid meningiomas from 30 patients was performed. Mutations in NF2 was detected in 18 cases (60%), LRP1B in 30%, TRAF7 in 27%, NF2 in 20%, ATM in 7% (1 germline and 1 somatic), in other genes in 47% (Georgescu et al., 2020).
    Somatic mutations: Tumors from 37 patients with pediatric low grade gliomas (31 pilocytic astrocytomas, 4 pleomorphic xanthoastrocytomas and 2 diffuse gliomas) were analyzed. Genetic alterations were found in 97% of cases, The KIAA1549 / BRAF fusion was the most common alteration (57%) followed by AFAP1/NTRK2 (5%) and TBL1XR1/PIK3CA (5%) fusions that were observed at much lower frequencies. The most frequently mutated genes were NOTCH genes (19%), ATM (11%), RAD51C, RNF43, SLX4, and NF1 (Mobark et al., 2020).
    Expression: In a study of 95 gliomas of different grades, the methylation index of a set of genes was tested. RASSF1A, RUNX3, GATA6, and MGMT were most frequently methylated, whereas the CDKN2A-CDKN2B locus, PTEN, RARB, and ATM were methylated to a lesser extent (Majchrzak-Celinska et al., 2015). One of the most important inactivation mechanisms of ATM gene is promoter methylation. 30 cases of different types of brain tumors (14 medulloblastoma, 6 astrocytoma, 7 glioblastoma multiforme (7), 3 others) were studied. ATM promoter was methylated in 73% of patients (Mehdipour et al., 2015). In a sample of 52 brain tumors, ATM, CCND2, TP53 and RB1 had higher expression in astrocytoma than in meningioma tumors. Higher grade astrocytoma tumors had up-regulation for CCND2 and ATM (Kheirollahi et al., 2011).
    Prognosis To identify the association between ATM somatic mutations and improved radio-sensitivity, 39 IDH-wildtype high-grade glioma (2 diffuse astrocytoma, 10 anaplastic astrocytoma, and 27 glioblastoma) were studied. ATM mutations were detected in 26% of cases (6 glioblastoma and 4 anaplastic astrocytoma cases). ATM mutations might be involved in the increased radio-sensitivity (Kim et al., 2020). Silencing of ATM expression via siRNA technique was found to improve radiosensitivity of glioma stem cell in vitro and in vivo (Li et al.. 2017).
      
      
    Entity Skin Melanoma
    Note Germline mutations: A large study involving more than 600,000 cancer patients with various cancers found that 0.7% patients had an ATM pathogenic variant. c.7271T>G was associated with higher melanoma risk (OR= 1.46; 95% CI, 1.18-1.81) (Hall et al., 2021).
    Expression: A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) and 59 cases of nevi (27 normal nevi and 32 dysplastic nevi) were studied. Phosphorylated ATM at serine-1981 was explored. Both loss of phospho-ATM expression, and high phospho-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma (normal nevi: 100% moderate expression, dysplastic nevi 81%, primary melanomas 73%, metastatic melanomas 60%). High phospho-ATM expression was correlated to the worse outcome at 5 and 10yrs, negative phospho-ATM expression was correlated with an intermediate survival at 5yrs, but a poor survival at 10yrs, comparable to high phospho-ATM expression cases. Moderate phospho-ATM expression was correlated with the best outcome (Bhandaru et al., 2015).
      
      
    Entity Uveal melanoma
    Note Expression of ATM was investigated in 69 choroid melanoma samples. Loss of ATM was observed in 65% of cases. Loss of ATM was associated with a poor prognosis. (Jha et al., 2019).
      
      
    Entity Soft tissue sarcomas
    Note Somatic mutations: Somatic mutations of ATM were found in 2 of 43 cases of myxofibrosarcoma and in 1 of 15 cases of undifferentiated spindle cell sarcoma, but not in undifferentiated pleomorphic sarcomas (0 of 18 cases) nor in dedifferentiated liposarcoma (0 of 6) (Lewin et al., 2018). Somatic mutations were found in 7 of 86 patients with liposarcoma (Kanojia et al., 2015).
    Expression: 17 cases of rhabdomyosarcoma specimens were studied and 7 of the 17 cases were negative for ATM expression (41%) (2 embryonal rhabdomyosarcoma, 1 alveolar rhabdomyosarcoma, and 4 "unknown subtype") (Zhang et al., 2003).
      
      
    Entity Chronic myelogenous leukemia (CML)
    Note Atm-knockout in p210Bcr/Abl1 transgenic mice resulted in the acceleration of the blast crisis, which supports that the DNA damage-response pathway plays a vital role for determination of susceptibility to blast crisis in CML (Takagi et al., 2013).
    Disease Chronic myelogenous leukemia (9975/3) is a myeloproliferative neoplasm
      
      
    Entity Acute myeloid leukemias
    Note MIR100 was highly expressed in bone marrow of pediatric acute myeloid leukemia (AML) patients and cell lines, and MIR100 depletion inhibits cell viability and induces cell apoptosis. The expression of ATM was downregulated in bone marrow of AML patients and AML cell lines whereas ectopic expression of ATM repressed cell viability while enhanced apoptosis. ATM is inhibited by MIR100 (Sun et al., 2020). MIR181A1 was overexpressed in pediatric AML, which showed an inverse association with ATM expression (Liu et al., 2016). 33 cases of blastic plasmacytoid dendritic cell neoplasm (9727/3) were studied. Somatic point mutations were found in NRAS (27% of cases), ATM (21%), MET, KRAS, IDH2, KIT (9% each), etc…
    Disease Acute myeloid leukaemia (AML) and related precursor neoplasms
      
      
    Entity Acute lymphoblastic leukemia
    Note A series of 57 childhood acute lymphoblastic leukemia (ALL) cases (26 B-precursor ALL and 31 T-ALL) were studied. 28 distinct ATM alterations were found in 14 patients (25%). Six alterations of potential biological significance were observed in 5 cases of B-precursor ALL (19%), and 5 were found in 3 cases of T-ALL (10%). In two cases of B-precursor ALL cases, the ATM alterations were germline (Gumy Pause et al., 2003). Chromothripsis was found in ALLs developing in patients with Ataxia Telangiectasia inherited disease (Ratnaparkhe et al., 2017).
    Disease Acute lymphoblastic leukemia is a precursor lymphoid neoplasm
      
      
    Entity Chronic lymphocytic leukemia
    Note Germline mutations: 516 cases plus additional cohorts of 106 exomes and24 genomes were studied. Two genes were significantly associated with chronic lymphocytic leukemia (CLL): CDK1 and ATM (Tiao et al., 2017).
    Germline/somatic mutations: In early studies, six CLL cases were studied. Both germ-line and somatic ATM mutations in CLL were found. The observed AT heterozygotes frequency of 6% in CLL was greater than the 1% estimate in the general population. 41 patients with CLL were studied for loss of heterozygosity. 14% had heterozygosity in ATM and a mutation in the second allele. Patients with ATM deficiency had significantly shorter survival times (Starostik et al. 1998; Bullrich F et al. 1999). 16 of 50 B-CLLs analyzed had ATM mutations (7 biallelic; 3 germline, 11 somatic, 6?), and 6 had mutations in TP53. All 16 ATM mutant B-CLLs showed the absence of somatic variable region heavy chain hypermutation indicating a pregerminal center cell origin (Stankovic T et al. 2002). Fifteen of 56 patients analyzed (27%) showed a pattern compatible with the presence of a somatic mutation (Lahdesmaki et al., 2004). can be found in 10% of patients with CLL in early stage and 20-25% in patients with advanced disease. About 40% of patients with a del(11q) have an inactivating mutation of the second ATM allele and these cases show a poor chemotherapy response. In addition, patients carrying a del(11q) clone typically show rapid progression, and reduced overall survival (review in Knittel et al., 2015). Samples from 54 patients with CLL were used. Twelve somatic mutations and 15 germline mutations were found. In the 12 CLL samples with somatic mutations, 8 were deficient in ATM function, while only one of the 15 CLL samples with only germline mutations had diminished ATM function, indicating that the germline mutations have minimal impact on ATM activity. Seventeen of the 26 samples with mutations retained ATM function. Patients with deficient ATM function had lesser progression-free survival than those with normal ATM function (Jiang et al., 2016). Patients with biallelic ATM alteration had shorter overall survival than patients with isolated del(11q), similar to patients with delTP53 (Lozano-Santos et al., 2017).
    Somatic mutations: 1,043 CLL patients were studied; 42% patients displayed abnormal karyotypes, and 10% had complex karyotypes. The group with complex karyotypes included patients with more advanced disease at diagnosis, including a higher proportion of patients diagnosed at Binet stage B/C, delATM (25% vs 7% in not-complex karyotypes) and delTP53 (40% vs 5%). Median overall survival was 87 months in delATM patients, 79 months in complex karyotypes patients, and 56 months in delTP53 patients. A subgroup of CLL patients with complex karyotypes lacking "high-risk-FISH abnormalities" (namely: delATM/delTP53) showed an equivalent impaired clinical evolution as those with high-risk-FISH abnormalities and no complex karyotypes (Puiggros et al., 2017). A cohort of 249 CLL patients was studied. ATM mutations were found in 19%. Short telomeres were significantly associated with both reduced time-to-first-treatment and overall survival in subset #2 (Note: focusing on rearrangements of IGH genes, subset #2 is defined by: mutational status: mostly mutated, IGHV: V3-21, IGHJ: J6, VH CDR3 length 9, pattern: [AVLI]x[DE]xxxM[DE]x, see Agathangelidis et al, 2012. The highest ATM mutation frequency was observed in subset #2, and was associated with particularly short telomeres (Navrkalova et al., 2016); In 499 CLL cases, ATM mutations were observed in 37 cases (7%), without evidence of any mutational hotspots. BIRC3, POT, BRAF, XPO1 and KRAS were also mutated in 7 to 6% of cases. Biallelic BIRC3 deleted patients had reduced overall survival in comparison to sole del(11q) patients, while ATM abnormalities did not significantly differ in median survival times compared with sole del(11q) cases (Blakemore et al., 2020). Unmutated IGHV genes are strongly associated with poor survival, while Binet stage A patients with mutated IGHV genes have a much better prognosis. 150 samples from patients with CLL were analyzed. Tumor mutational burden (or mutational complexity) can be evaluated from an eight gene estimator that comprises ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53. Median tumor mutational burden was 1.75. ATM, SF3B1, NOTCH1 and BIRC3 were the genes the most frequently mutated. Tumor mutational burden evaluated from the eight gene estimator was significantly higher in high risk (del(11q), or complex karyotype) than in low risk (isolated or normal karyotype) cytogenetic categories and was strongly associated with cytogenetic complexity. Any mutation in this set of 8 genes is associated with poor prognosis cytogenetics (eg, del(11q), del(17p) and complex karyotype) as well as with unmutated IGHV genes. Tumor mutational burden also predicted shorter treatment-free survival even in Binet stage A patients or patients with a good prognosis karyotype. These results indicate that Binet stage, IGHV mutational status, and tumor mutational burden identify patients at diagnosis who will need to be rapidly treated despite a clinically non-progressive disease. Tumor mutational burden could also help to predict evolution of patients in Binet stage A or with good prognosis cytogenetics (Chauzeix et al., 2020).
    Disease Chronic lymphocytic leukemia (9823/3) is a mature B-cell neoplasm.
    Oncogenesis Combination Sf3b1 mutation with Atm deletion in mouse B cells leads to the overcoming of cellular senescence and the development of CLL-like disease in elderly mice (Yin et al., 2019).
      
      
    Entity Diffuse large B-cell lymphoma
    Note Atm deficiency promotes development of murine B-cell lymphomas that resemble diffuse large B-cell lymphoma (Hathcock et al., 2015).
    Disease Diffuse large B-cell lymphoma (9680/3) is a mature B-cell neoplasm.
      
      
    Entity Mantle cell lymphoma
    Note ATM is the most frequently mutated gene in mantle cell lymphoma (MCL) (about 50%) (Swerdlow et al , 2008). ATM mutation in MCL is mostly of somatic origin.
    In an early study, 8 ATM gene mutations were detected in 7 of 20 patients with mantle cell lymphoma. Somatic origin was demonstrated in 3 cases, and one mutation was germline. Chromosomal imbalances were significantly higher in typical MCL with ATM inactivation (Camacho et al., 2002). ATM and TP53 mutations in 72 MCL patients were analyzed. Mutated ATM and TP53 alleles were found in 51% and 22% respectively, with only three patients harboring mutations in both genes. Mutated TP53 gene was associated with a reduced overall survival (Mareckova et al., 2019). A total of 552 patients samples from six studies published in the literature were reviewed. Somatic mutations in ATM (40-50%), CCND1 (14-35%), TP53 (7-31%), KMT2D (12-20%), KMT2C (16%), NOTCH1 (5-14%), NSD2 (7-13%), BIRC3 (5-10%), UBR5 (7-18%) were most frequently encountered in mantle cell lymphoma (Ahmed et al. 2016). Data were extracted from 2,045 MCL patients in another meta-analysis of 32 selected articles. The mutations detected are likely to be somatic, but data is missing concerning the possibility of germline mutations. ATM was the most frequently mutated gene (44%) at diagnosis, followed by IGH (38%), TP53 (27%), CDKN2A (24%), MYC (21%), and CCND1 (20%). During disease progression the level of mutations increases. The highest increases were found in TP53 (+16%), ATM (+14%), KMT2A (+13%), MAP3K14 (+12%), BTK (+12%), TRAF2 (+11%). (Hill et al, 2020).
    Disease Mantle cell lymphoma (9673/3) is a mature B-cell neoplasm.
    Prognosis Mantle cell lymphoma (MCL) cells deficient in both ATM and TP53 are more sensitive to PARP inhibitors than cells lacking ATM function alone. Combining inhibitors of PARP and ATM may have utility in TP53-deficient MCL (Williamson et al., 2012)
      
      
    Entity Splenic marginal-zone B-cell lymphoma
    Note Absence of ATM deletions in 16 cases of splenic marginal-zone B-cell lymphoma was noted (Salido et al., 2003).
    Disease Splenic marginal-zone B-cell lymphoma (9689/3) is a mature B-cell neoplasm.
      
      
    Entity Non-Hodgkin lymphomas
    Note Twenty-seven cases of childhood non-Hodgkin lymphoma (NHL) were screened. ATM alterations were detected in 12 cases. there were 13 B-cell NHL NOS (with 2 pathogenic mutations, 2 polymorphisms); 7 Burkitt lymphoma (2 pathogenic mutations, 1 reduced protein expression, 2 polymorphisms); 1 diffuse large B-cell lymphoma (1 pathogenic mutation); 2 T-lymphoblastic lymphoma (1 pathogenic mutation); 2 T-cell non-Hodgkin lymphoma (1 polymorphism), and 1 lymphoblastic lymphoma and 1 NHL-NOS. ATM methylation status was normal (Gumy-Pause et al., 2006). In a population of 1,297 NHL cases and 1,946 controls, ATM polymorphisms were associated with diffuse large B-cell lymphoma (412 cases) and CLL (164 cases), in particular rs227060, but not with follicular lymphomas (301 cases) (Rendleman et al., 2014).
    Disease Non-Hodgkin lymphomas are either mature B-cell neoplasms or mature T- and NK-cell neoplasms.
      
      
    Entity T-cell acute lymphoblastic leukemia
    Note Somatic inactivation of Atm in hematopoietic cells predisposes mice to T-cell acute lymphoblastic leukemia and Ccnd3 was necessary for initiation of T-ALLs (Ehrlich et al., 2015).
    Disease T-cell acute lymphoblastic leukemia (9827/3) is a mature T- and NK-cell neoplasm.
      
      
    Entity T-cell prolymphocytic leukemia
    Note Mutations of ATM was found in 17 of 37 patients with T prolymphocytic leukemia (T-PLL). Two of seventeen mutated T-PLL samples had a previously reported A-T allele (Vorechovsky et al., 1997). In a panel of eight cases of T-cell prolymphocytic leukemia, there were structural lesions of ATM in all samples, and in four samples both alleles were affected (Yuille et al., 1998). Among 25 T-cell prolymphocytic leukemia cases, gain of MYC (67%), loss of ATM (64%), and gain (75%) and/or rearrangement (78%) of TCL1A were found (Hsi et al., 2014). In another study, 70% of 40 T-PLL samples harbored somatic mutations in the tumor suppressor ATM (Kiel et al., 2014).
    Disease T-cell prolymphocytic leukemia (9834/3) is a mature T- and NK-cell neoplasm.
      
      
    Entity Peripheral T cell lymphoma
    Note Matched peripheral T cell lymphomas and non-malignant samples from 12 patients revealed 104 somatic mutations. Somatic mutations in ATM were found in 5 out of the 12 patients (Simpson et al., 2015). Mutations in ATM were also found in a panel of 125 peripheral T cell lymphomas (Palomero et al., 2014).
    Disease Peripheral T cell lymphoma (9702/3) is a mature T- and NK-cell neoplasm.
      
      
    Entity Extranodal natural killer/T cell lymphoma
    Note The expression of ATM in nasal extranodal NK/T cell lymphoma was decreased compared with that in nasal benign lymphoid proliferative disease (Ye et al., 2021). Phospho-ATM (pATM) (Ser1981) was distinguishingly expressed in eleven of the 12 cases of extranodal natural killer/T cell lymphoma, while pATM was negative in all normal lymph nodes (Sui et al., 2020).
    Disease Extranodal NK/T cell lymphoma is a mature T- and NK-cell neoplasm.
      
      
    Entity Hodgkin lymphoma
    Note Tumors were obtained from 23 children with Hodgkin disease. Two patients (9%) had germline mutation, and both had a more aggressive disease. Four out of 12 informative patients exhibited loss of heterozygosity centromeric to ATM locus. Polymorphisms were also detected (Liberzon et al., 2004).
      

    Bibliography

    Malignancies in pediatric patients with ataxia telangiectasia
    Murphy RC, Berdon WE, Ruzal-Shapiro C, Hall EJ, Kornecki A, Daneman A, Brunelle F, Campbell JB
    Pediatr Radiol 1999 Apr;29(4):225-30.
    PMID 10199897
     
    Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families
    Janin N, Andrieu N, Ossian K, Laugé A, Croquette MF, Griscelli C, Debré M, Bressac-de-Paillerets B, Aurias A, Stoppa-Lyonnet D
    Br J Cancer 1999 Jun;80(7):1042-5.
    PMID 10362113
     
    Identification of ataxia telangiectasia heterozygotes, a cancer-prone population, using the single-cell gel electrophoresis (Comet) assay
    Djuzenova CS, Schindler D, Stopper H, Hoehn H, Flentje M, Oppitz U
    Lab Invest 1999 Jun;79(6):699-705.
    PMID 10378512
     
    Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs
    Barlow C, Dennery PA, Shigenaga MK, Smith MA, Morrow JD, Roberts LJ, Wynshaw-Boris A, Levine RL
    Proc Natl Acad Sci U S A 1999 Aug 17;96(17):9915-9.
    PMID 10449794
     
    Altered telomere nuclear matrix interactions and nucleosomal periodicity in ataxia telangiectasia cells before and after ionizing radiation treatment
    Smilenov LB, Dhar S, Pandita TK
    Mol Cell Biol 1999 Oct;19(10):6963-71.
    PMID 10490633
     
    Localization of a portion of extranuclear ATM to peroxisomes
    Watters D, Kedar P, Spring K, Bjorkman J, Chen P, Gatei M, Birrell G, Garrone B, Srinivasa P, Crane DI, Lavin MF
    J Biol Chem 1999 Nov 26;274(48):34277-82.
    PMID 10567403
     
    Oligo-/monoclonal gammopathy and hypergammaglobulinemia in ataxia-telangiectasia. A study of 90 patients
    Sadighi Akha AA, Humphrey RL, Winkelstein JA, Loeb DM, Lederman HM
    Medicine (Baltimore) 1999 Nov;78(6):370-81.
    PMID 10575419
     
    Oropharyngeal dysphagia and aspiration in patients with ataxia-telangiectasia
    Lefton-Greif MA, Crawford TO, Winkelstein JA, Loughlin GM, Koerner CB, Zahurak M, Lederman HM
    J Pediatr 2000 Feb;136(2):225-31.
    PMID 10657830
     
    ATM-heterozygous germline mutations contribute to breast cancer-susceptibility
    Broeks A, Urbanus JH, Floore AN, Dahler EC, Klijn JG, Rutgers EJ, Devilee P, Russell NS, van Leeuwen FE, van ', t Veer LJ
    Am J Hum Genet 2000 Feb;66(2):494-500.
    PMID 10677309
     
    Quantitative neurologic assessment of ataxia-telangiectasia
    Crawford TO, Mandir AS, Lefton-Greif MA, Goodman SN, Goodman BK, Sengul H, Lederman HM
    Neurology 2000 Apr 11;54(7):1505-9.
    PMID 10751267
     
    Protective roles for ATM in cellular response to oxidative stress
    Takao N, Li Y, Yamamoto K
    FEBS Lett 2000 Apr 21;472(1):133-6.
    PMID 10781820
     
    Lymphoid malignancy as a presenting sign of ataxia-telangiectasia
    Loeb DM, Lederman HM, Winkelstein JA
    J Pediatr Hematol Oncol Sep-Oct 2000;22(5):464-7.
    PMID 11037863
     
    Mortality rates among carriers of ataxia-telangiectasia mutant alleles
    Su Y, Swift M
    Ann Intern Med 2000 Nov 21;133(10):770-8.
    PMID 11085839
     
    Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1
    Yang DQ, Kastan MB
    Nat Cell Biol 2000 Dec;2(12):893-8.
    PMID 11146653
     
    ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response
    Peretz S, Jensen R, Baserga R, Glazer PM
    Proc Natl Acad Sci U S A 2001 Feb 13;98(4):1676-81.
    PMID 11172010
     
    Mutagen sensitivity of human lymphoblastoid cells with a BRCA1 mutation in comparison to ataxia telangiectasia heterozygote cells
    Speit G, Trenz K, Schütz P, Bendix R, Dörk T
    Cytogenet Cell Genet 2000;91(1-4):261-6.
    PMID 11173867
     
    Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries
    Olsen JH, Hahnemann JM, Børresen-Dale AL, Brøndum-Nielsen K, Hammarström L, Kleinerman R, Kääriäinen H, Lönnqvist T, Sankila R, Seersholm N, Tretli S, Yuen J, Boice JD, Tucker M
    J Natl Cancer Inst 2001 Jan 17;93(2):121-7.
    PMID 11208881
     
    Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2
    Lee SA, Dritschilo A, Jung M
    J Biol Chem 2001 Apr 13;276(15):11783-90.
    PMID 11278277
     
    Increased oxidative stress in ataxia telangiectasia evidenced by alterations in redox state of brains from Atm-deficient mice
    Kamsler A, Daily D, Hochman A, Stern N, Shiloh Y, Rotman G, Barzilai A
    Cancer Res 2001 Mar 1;61(5):1849-54.
    PMID 11280737
     
    Characterization of ataxia telangiectasia fibroblasts with extended life-span through telomerase expression
    Wood LD, Halvorsen TL, Dhar S, Baur JA, Pandita RK, Wright WE, Hande MP, Calaf G, Hei TK, Levine F, Shay JW, Wang JJ, Pandita TK
    Oncogene 2001 Jan 18;20(3):278-88.
    PMID 11313956
     
    Ataxia-telangiectasia: chronic activation of damage-responsive functions is reduced by alpha-lipoic acid
    Gatei M, Shkedy D, Khanna KK, Uziel T, Shiloh Y, Pandita TK, Lavin MF, Rotman G
    Oncogene 2001 Jan 18;20(3):289-94.
    PMID 11313957
     
    Spontaneously immortalized cell lines obtained from adult Atm null mice retain sensitivity to ionizing radiation and exhibit a mutational pattern suggestive of oxidative stress
    Gage BM, Alroy D, Shin CY, Ponomareva ON, Dhar S, Sharma GG, Pandita TK, Thayer MJ, Turker MS
    Oncogene 2001 Jul 19;20(32):4291-7.
    PMID 11466609
     
    ATM phosphorylates histone H2AX in response to DNA double-strand breaks
    Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ
    J Biol Chem 2001 Nov 9;276(45):42462-7.
    PMID 11571274
     
    Ataxia telangiectasia mutated-deficient B-cell chronic lymphocytic leukemia occurs in pregerminal center cells and results in defective damage response and unrepaired chromosome damage
    Stankovic T, Stewart GS, Fegan C, Biggs P, Last J, Byrd PJ, Keenan RD, Moss PA, Taylor AM
    Blood 2002 Jan 1;99(1):300-9.
    PMID 11756185
     
    Breakpoints in the ataxia telangiectasia gene arise at the RGYW somatic hypermutation motif
    Bradshaw PS, Condie A, Matutes E, Catovsky D, Yuille MR
    Oncogene 2002 Jan 17;21(3):483-7.
    PMID 11821961
     
    Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity
    Taylor AM, Harnden DG, Arlett CF, Harcourt SA, Lehmann AR, Stevens S, Bridges BA
    Nature 1975 Dec 4;258(5534):427-9.
    PMID 1196376
     
    Elevated oxidative stress in patients with ataxia telangiectasia
    Reichenbach J, Schubert R, Schindler D, Müller K, Böhles H, Zielen S
    Antioxid Redox Signal 2002 Jun;4(3):465-9.
    PMID 12215213
     
    Deficiency in the repair of UV-induced DNA damage in human skin fibroblasts compromised for the ATM gene
    Hannan MA, Hellani A, Al-Khodairy FM, Kunhi M, Siddiqui Y, Al-Yussef N, Pangue-Cruz N, Siewertsen M, Al-Ahdal MN, Aboussekhra A
    Carcinogenesis 2002 Oct;23(10):1617-24.
    PMID 12376469
     
    ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage
    Barzilai A, Rotman G, Shiloh Y
    DNA Repair (Amst) 2002 Jan 22;1(1):3-25.
    PMID 12509294
     
    DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Bakkenist CJ, Kastan MB
    Nature 2003 Jan 30;421(6922):499-506.
    PMID 12556884
     
    Defective excision repair of gamma-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts
    Paterson MC, Smith BP, Lohman PH, Anderson AK, Fishman L
    Nature 1976 Apr 1;260(5550):444-7.
    PMID 1256588
     
    Oxidative stress in ataxia telangiectasia
    Watters DJ
    Redox Rep 2003;8(1):23-9.
    PMID 12631440
     
    Association of ataxia telangiectasia mutated (ATM) gene mutation/deletion with rhabdomyosarcoma
    Zhang P, Bhakta KS, Puri PL, Newbury RO, Feramisco JR, Wang JY
    Cancer Biol Ther Jan-Feb 2003;2(1):87-91.
    PMID 12673126
     
    ATM gene alterations in childhood acute lymphoblastic leukemias
    Gumy Pause F, Wacker P, Maillet P, Betts D, Sappino AP
    Hum Mutat 2003 May;21(5):554.
    PMID 12673804
     
    Loss of atm sensitises p53-deficient cells to topoisomerase poisons and antimetabolites
    Fedier A, Schlamminger M, Schwarz VA, Haller U, Howell SB, Fink D
    Ann Oncol 2003 Jun;14(6):938-45.
    PMID 12796033
     
    Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection
    BODER E, SEDGWICK RP
    Pediatrics 1958 Apr;21(4):526-54.
    PMID 13542097
     
    Progressive ataxia in childhood with particular reference to ataxia-telangiectasia
    SEDGWICK RP, BODER E
    Neurology 1960 Jul;10:705-15.
    PMID 14444443
     
    Absence of ATM deletions in 16 cases of splenic marginal-zone B-cell lymphoma (SMZBCL)
    Salido M, Astier L, Puigdecanet E, Espinet B, Florensa L, Solé F
    Haematologica 2003 Nov;88(11):ELT33.
    PMID 14607769
     
    Oxidative stress is responsible for deficient survival and dendritogenesis in purkinje neurons from ataxia-telangiectasia mutated mutant mice
    Chen P, Peng C, Luff J, Spring K, Watters D, Bottle S, Furuya S, Lavin MF
    J Neurosci 2003 Dec 10;23(36):11453-60.
    PMID 14673010
     
    Molecular variants of the ATM gene in Hodgkin's disease in children
    Liberzon E, Avigad S, Yaniv I, Stark B, Avrahami G, Goshen Y, Zaizov R
    Br J Cancer 2004 Jan 26;90(2):522-5.
    PMID 14735203
     
    ATM mutations in B-cell chronic lymphocytic leukemia
    Lähdesmäki A, Kimby E, Duke V, Foroni L, Hammarström L
    Haematologica 2004 Jan;89(1):109-10.
    PMID 14754616
     
    Immunodeficiency and infections in ataxia-telangiectasia
    Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM
    J Pediatr 2004 Apr;144(4):505-11.
    PMID 15069401
     
    Ataxia-telangiectasia, an evolving phenotype
    Chun HH, Gatti RA
    DNA Repair (Amst) Aug-Sep 2004;3(8-9):1187-96.
    PMID 15279807
     
    Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice
    Reliene R, Fischer E, Schiestl RH
    Cancer Res 2004 Aug 1;64(15):5148-53.
    PMID 15289318
     
    Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM
    Viniegra JG, Martínez N, Modirassari P, Hernández Losa J, Parada Cobo C, Sánchez-Arévalo Lobo VJ, Aceves Luquero CI, Alvarez-Vallina L, Ramón y Cajal S, Rojas JM, Sánchez-Prieto R
    J Biol Chem 2005 Feb 11;280(6):4029-36.
    PMID 15546863
     
    ATM activation in normal human tissues and testicular cancer
    Bartkova J, Bakkenist CJ, Rajpert-De Meyts E, Skakkebaek NE, Sehested M, Lukas J, Kastan MB, Bartek J
    Cell Cycle 2005 Jun;4(6):838-45.
    PMID 15846060
     
    Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice
    Wu D, Yang H, Xiang W, Zhou L, Shi M, Julies G, Laplante JM, Ballard BR, Guo Z
    J Lipid Res 2005 Jul;46(7):1380-7.
    PMID 15863839
     
    Identification of domains of ataxia-telangiectasia mutated required for nuclear localization and chromatin association
    Young DB, Jonnalagadda J, Gatei M, Jans DA, Meyn S, Khanna KK
    J Biol Chem 2005 Jul 29;280(30):27587-94.
    PMID 15929992
     
    ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1
    You Z, Chahwan C, Bailis J, Hunter T, Russell P
    Mol Cell Biol 2005 Jul;25(13):5363-79.
    PMID 15964794
     
    Impaired genomic stability and increased oxidative stress exacerbate different features of Ataxia-telangiectasia
    Ziv S, Brenner O, Amariglio N, Smorodinsky NI, Galron R, Carrion DV, Zhang W, Sharma GG, Pandita RK, Agarwal M, Elkon R, Katzin N, Bar-Am I, Pandita TK, Kucherlapati R, Rechavi G, Shiloh Y, Barzilai A
    Hum Mol Genet 2005 Oct 1;14(19):2929-43.
    PMID 16150740
     
    Genome instability in ataxia telangiectasia (A-T) families: camptothecin-induced damage to replicating DNA discriminates between obligate A-T heterozygotes, A-T homozygotes and controls
    Leonard JC, Mullinger AM, Schmidt J, Cordell HJ, Johnson RT
    Biosci Rep 2004 Dec;24(6):617-29.
    PMID 16158199
     
    ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes
    Liu N, Stoica G, Yan M, Scofield VL, Qiang W, Lynn WS, Wong PK
    Lab Invest 2005 Dec;85(12):1471-80.
    PMID 16189515
     
    Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk
    Kim JH, Kim H, Lee KY, Choe KH, Ryu JS, Yoon HI, Sung SW, Yoo KY, Hong YC
    Hum Mol Genet 2006 Apr 1;15(7):1181-6.
    PMID 16497724
     
    ATM alterations in childhood non-Hodgkin lymphoma
    Gumy-Pause F, Wacker P, Maillet P, Betts DR, Sappino AP
    Cancer Genet Cytogenet 2006 Apr 15;166(2):101-11.
    PMID 16631465
     
    Involvement of novel autophosphorylation sites in ATM activation
    Kozlov SV, Graham ME, Peng C, Chen P, Robinson PJ, Lavin MF
    EMBO J 2006 Aug 9;25(15):3504-14.
    PMID 16858402
     
    ATM and breast cancer susceptibility
    Ahmed M, Rahman N
    Oncogene 2006 Sep 25;25(43):5906-11.
    PMID 16998505
     
    ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
    Schneider JG, Finck BN, Ren J, Standley KN, Takagi M, Maclean KH, Bernal-Mizrachi C, Muslin AJ, Kastan MB, Semenkovich CF
    Cell Metab 2006 Nov;4(5):377-89.
    PMID 17084711
     
    Genetic variation in p53 and ATM haplotypes and risk of glioma and meningioma
    Malmer BS, Feychting M, Lönn S, Lindström S, Grönberg H, Ahlbom A, Schwartzbaum J, Auvinen A, Collatz-Christensen H, Johansen C, Kiuru A, Mudie N, Salminen T, Schoemaker MJ, Swerdlow AJ, Henriksson R
    J Neurooncol 2007 May;82(3):229-37.
    PMID 17151932
     
    Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice
    Reliene R, Schiestl RH
    J Nutr 2007 Jan;137(1 Suppl):229S-232S.
    PMID 17182831
     
    Ataxia-telangiectasia-mutated-dependent activation of Ku in human fibroblasts exposed to hydrogen peroxide
    Lee JH, Kim KH, Morio T, Kim H
    Ann N Y Acad Sci 2006 Dec;1091:76-82.
    PMID 17341604
     
    Impaired insulin secretion in a mouse model of ataxia telangiectasia
    Miles PD, Treuner K, Latronica M, Olefsky JM, Barlow C
    Am J Physiol Endocrinol Metab 2007 Jul;293(1):E70-4.
    PMID 17356010
     
    A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints
    Mu JJ, Wang Y, Luo H, Leng M, Zhang J, Yang T, Besusso D, Jung SY, Qin J
    J Biol Chem 2007 Jun 15;282(24):17330-4.
    PMID 17478428
     
    ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ
    Science 2007 May 25;316(5828):1160-6.
    PMID 17525332
     
    The cytogenetics of ataxia telangiectasia
    Kojis TL, Gatti RA, Sparkes RS
    Cancer Genet Cytogenet 1991 Oct 15;56(2):143-56.
    PMID 1756458
     
    ATM sequence variants associate with susceptibility to non-small cell lung cancer
    Yang H, Spitz MR, Stewart DJ, Lu C, Gorlov IP, Wu X
    Int J Cancer 2007 Nov 15;121(10):2254-9.
    PMID 17582598
     
    Intrinsic mitochondrial dysfunction in ATM-deficient lymphoblastoid cells
    Ambrose M, Goldstine JV, Gatti RA
    Hum Mol Genet 2007 Sep 15;16(18):2154-64.
    PMID 17606465
     
    Ataxia-telangiectasia: mild neurological presentation despite null ATM mutation and severe cellular phenotype
    Alterman N, Fattal-Valevski A, Moyal L, Crawford TO, Lederman HM, Ziv Y, Shiloh Y
    Am J Med Genet A 2007 Aug 15;143A(16):1827-34.
    PMID 17632790
     
    Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis
    Eaton JS, Lin ZP, Sartorelli AC, Bonawitz ND, Shadel GS
    J Clin Invest 2007 Sep;117(9):2723-34.
    PMID 17786248
     
    DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity
    Sun Y, Xu Y, Roy K, Price BD
    Mol Cell Biol 2007 Dec;27(24):8502-9.
    PMID 17923702
     
    Expression status of ataxia-telangiectasia-mutated gene correlated with prognosis in advanced gastric cancer
    Kang B, Guo RF, Tan XH, Zhao M, Tang ZB, Lu YY
    Mutat Res 2008 Feb 1;638(1-2):17-25.
    PMID 17928013
     
    The DNA damage signalling kinase ATM is aberrantly reduced or lost in BRCA1/BRCA2-deficient and ER/PR/ERBB2-triple-negative breast cancer
    Tommiska J, Bartkova J, Heinonen M, Hautala L, Kilpivaara O, Eerola H, Aittomäki K, Hofstetter B, Lukas J, von Smitten K, Blomqvist C, Ristimäki A, Heikkilä P, Bartek J, Nevanlinna H
    Oncogene 2008 Apr 10;27(17):2501-6.
    PMID 17982490
     
    Chemical mutagen hypersensitivity in ataxia telangiectasia
    Hoar DI, Sargent P
    Nature 1976 Jun 17;261(5561):590-2.
    PMID 180416
     
    Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation
    Fu X, Wan S, Lyu YL, Liu LF, Qi H
    PLoS One 2008 Apr 23;3(4):e2009.
    PMID 18431490
     
    Different clinical and immunological presentation of ataxia-telangiectasia within the same family
    Soresina A, Meini A, Lougaris V, Cattaneo G, Pellegrino S, Piane M, Darra F, Plebani A
    Neuropediatrics 2008 Feb;39(1):43-5.
    PMID 18504682
     
    ATM protein kinase mediates full activation of Akt and regulates glucose transporter 4 translocation by insulin in muscle cells
    Halaby MJ, Hibma JC, He J, Yang DQ
    Cell Signal 2008 Aug;20(8):1555-63.
    PMID 18534819
     
    Are the so-called low penetrance breast cancer genes, ATM, BRIP1, PALB2 and CHEK2, high risk for women with strong family histories?
    Byrnes GB, Southey MC, Hopper JL
    Breast Cancer Res 2008;10(3):208.
    PMID 18557994
     
    Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
    Lavin MF
    Nat Rev Mol Cell Biol 2008 Oct;9(10):759-69.
    PMID 18813293
     
    Somatic mutations affect key pathways in lung adenocarcinoma
    Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, Fulton L, Fulton RS, Zhang Q, Wendl MC, Lawrence MS, Larson DE, Chen K, Dooling DJ, Sabo A, Hawes AC, Shen H, Jhangiani SN, Lewis LR, Hall O, Zhu Y, Mathew T, Ren Y, Yao J, Scherer SE, Clerc K, Metcalf GA, Ng B, Milosavljevic A, Gonzalez-Garay ML, Osborne JR, Meyer R, Shi X, Tang Y, Koboldt DC, Lin L, Abbott R, Miner TL, Pohl C, Fewell G, Haipek C, Schmidt H, Dunford-Shore BH, Kraja A, Crosby SD, Sawyer CS, Vickery T, Sander S, Robinson J, Winckler W, Baldwin J, Chirieac LR, Dutt A, Fennell T, Hanna M, Johnson BE, Onofrio RC, Thomas RK, Tonon G, Weir BA, Zhao X, Ziaugra L, Zody MC, Giordano T, Orringer MB, Roth JA, Spitz MR, Wistuba II, Ozenberger B, Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M, Broderick S, Yoshizawa A, Travis WD, Pao W, Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander ES, Gibbs RA, Meyerson M, Wilson RK
    Nature 2008 Oct 23;455(7216):1069-75.
    PMID 18948947
     
    Modeling ATM mutant proteins from missense changes confirms retained kinase activity
    Barone G, Groom A, Reiman A, Srinivasan V, Byrd PJ, Taylor AM
    Hum Mutat 2009 Aug;30(8):1222-30.
    PMID 19431188
     
    Common mechanisms of PIKK regulation
    Lovejoy CA, Cortez D
    DNA Repair (Amst) 2009 Sep 2;8(9):1004-8.
    PMID 19464237
     
    Clinical spectrum of ataxia-telangiectasia in adulthood
    Verhagen MM, Abdo WF, Willemsen MA, Hogervorst FB, Smeets DF, Hiel JA, Brunt ER, van Rijn MA, Majoor Krakauer D, Oldenburg RA, Broeks A, Last JI, van', t Veer LJ, Tijssen MA, Dubois AM, Kremer HP, Weemaes CM, Taylor AM, van Deuren M
    Neurology 2009 Aug 11;73(6):430-7.
    PMID 19535770
     
    Incidence of cancer in 161 families affected by ataxia-telangiectasia
    Swift M, Morrell D, Massey RB, Chase CL
    N Engl J Med 1991 Dec 26;325(26):1831-6.
    PMID 1961222
     
    Common genetic changes in leiomyosarcoma and gastrointestinal stromal tumour: implication for ataxia telangiectasia mutated involvement
    Ul-Hassan A, Sisley K, Hughes D, Hammond DW, Robinson MH, Reed MW
    Int J Exp Pathol 2009 Oct;90(5):549-57.
    PMID 19765109
     
    Role of ataxia telangiectasia mutated in insulin signalling of muscle-derived cell lines and mouse soleus
    Jeong I, Patel AY, Zhang Z, Patil PB, Nadella ST, Nair S, Ralston L, Hoormann JK, Fisher JS
    Acta Physiol (Oxf) 2010 Apr;198(4):465-75.
    PMID 20003097
     
    ATM polymorphisms and risk of lung cancer among never smokers
    Lo YL, Hsiao CF, Jou YS, Chang GC, Tsai YH, Su WC, Chen YM, Huang MS, Chen HL, Yang PC, Chen CJ, Hsiung CA
    Lung Cancer 2010 Aug;69(2):148-54.
    PMID 20004998
     
    Expression of cyclin D2, P53, Rb and ATM cell cycle genes in brain tumors
    Kheirollahi M, Mehr-Azin M, Kamalian N, Mehdipour P
    Med Oncol 2011 Mar;28(1):7-14.
    PMID 20077038
     
    ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
    Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, Mills GB, Kastan MB, Walker CL
    Proc Natl Acad Sci U S A 2010 Mar 2;107(9):4153-8.
    PMID 20160076
     
    Homozygosity for c 6325T>G transition in the ATM gene causes an atypical, late-onset variant form of ataxia-telangiectasia
    Silvestri G, Masciullo M, Piane M, Savio C, Modoni A, Santoro M, Chessa L
    J Neurol 2010 Oct;257(10):1738-40.
    PMID 20480175
     
    ATM engages the TSC2/mTORC1 signaling node to regulate autophagy
    Alexander A, Kim J, Walker CL
    Autophagy 2010 Jul;6(5):672-3.
    PMID 20581436
     
    DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome
    Mercer JR, Cheng KK, Figg N, Gorenne I, Mahmoudi M, Griffin J, Vidal-Puig A, Logan A, Murphy MP, Bennett M
    Circ Res 2010 Oct 15;107(8):1021-31.
    PMID 20705925
     
    Differential localization of ATM is correlated with activation of distinct downstream signaling pathways
    Alexander A, Walker CL
    Cell Cycle 2010 Sep 15;9(18):3685-6.
    PMID 20890104
     
    ATM activation by oxidative stress
    Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT
    Science 2010 Oct 22;330(6003):517-21.
    PMID 20966255
     
    Association between DNA repair gene ATM polymorphisms and oral cancer susceptibility
    Bau DT, Chang CH, Tsai MH, Chiu CF, Tsou YA, Wang RF, Tsai CW, Tsai RY
    Laryngoscope 2010 Dec;120(12):2417-22.
    PMID 21108427
     
    ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage
    Bensimon A, Schmidt A, Ziv Y, Elkon R, Wang SY, Chen DJ, Aebersold R, Shiloh Y
    Sci Signal 2010 Dec 7;3(151):rs3.
    PMID 21139141
     
    ATM activation in the presence of oxidative stress
    Guo Z, Deshpande R, Paull TT
    Cell Cycle 2010 Dec 15;9(24):4805-11.
    PMID 21150274
     
    ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair
    Cosentino C, Grieco D, Costanzo V
    EMBO J 2011 Feb 2;30(3):546-55.
    PMID 21157431
     
    Iron loading and oxidative stress in the Atm-/- mouse liver
    McDonald CJ, Ostini L, Wallace DF, John AN, Watters DJ, Subramaniam VN
    Am J Physiol Gastrointest Liver Physiol 2011 Apr;300(4):G554-60.
    PMID 21292994
     
    Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
    Polo SE, Jackson SP
    Genes Dev 2011 Mar 1;25(5):409-33.
    PMID 21363960
     
    Ataxia telangiectasia mutated kinase plays a protective role in β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling
    Foster CR, Singh M, Subramanian V, Singh K
    Mol Cell Biochem 2011 Jul;353(1-2):13-22.
    PMID 21404020
     
    Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia
    Exley AR, Buckenham S, Hodges E, Hallam R, Byrd P, Last J, Trinder C, Harris S, Screaton N, Williams AP, Taylor AM, Shneerson JM
    Clin Immunol 2011 Jul;140(1):26-36.
    PMID 21459046
     
    ATM-dependent IGF-1 induction regulates secretory clusterin expression after DNA damage and in genetic instability
    Goetz EM, Shankar B, Zou Y, Morales JC, Luo X, Araki S, Bachoo R, Mayo LD, Boothman DA
    Oncogene 2011 Sep 1;30(35):3745-54.
    PMID 21460853
     
    ATM is a redox sensor linking genome stability and carbon metabolism
    Krüger A, Ralser M
    Sci Signal 2011 Apr 5;4(167):pe17.
    PMID 21467295
     
    ATM protein kinase: the linchpin of cellular defenses to stress
    Bhatti S, Kozlov S, Farooqi AA, Naqi A, Lavin M, Khanna KK
    Cell Mol Life Sci 2011 Sep;68(18):2977-3006.
    PMID 21533982
     
    Beyond ATM: the protein kinase landscape of the DNA damage response
    Bensimon A, Aebersold R, Shiloh Y
    FEBS Lett 2011 Jun 6;585(11):1625-39.
    PMID 21570395
     
    ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair
    Segal-Raz H, Mass G, Baranes-Bachar K, Lerenthal Y, Wang SY, Chung YM, Ziv-Lehrman S, Ström CE, Helleday T, Hu MC, Chen DJ, Shiloh Y
    EMBO Rep 2011 Jul 1;12(7):713-9.
    PMID 21637298
     
    Alterations of ATM and CADM1 in chromosomal 11q22.3-23.2 region are associated with the development of invasive cervical carcinoma
    Mazumder Indra D, Mitra S, Roy A, Mondal RK, Basu PS, Roychoudhury S, Chakravarty R, Panda CK
    Hum Genet 2011 Dec;130(6):735-48.
    PMID 21643982
     
    ATM protects against oxidative stress induced by oxidized low-density lipoprotein
    Semlitsch M, Shackelford RE, Zirkl S, Sattler W, Malle E
    DNA Repair (Amst) 2011 Aug 15;10(8):848-60.
    PMID 21669554
     
    Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours
    Reiman A, Srinivasan V, Barone G, Last JI, Wootton LL, Davies EG, Verhagen MM, Willemsen MA, Weemaes CM, Byrd PJ, Izatt L, Easton DF, Thompson DJ, Taylor AM
    Br J Cancer 2011 Aug 9;105(4):586-91.
    PMID 21792198
     
    Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage
    Zolner AE, Abdou I, Ye R, Mani RS, Fanta M, Yu Y, Douglas P, Tahbaz N, Fang S, Dobbs T, Wang C, Morrice N, Hendzel MJ, Weinfeld M, Lees-Miller SP
    Nucleic Acids Res 2011 Nov;39(21):9224-37.
    PMID 21824916
     
    Ataxia-telangiectasia
    Perlman SL, Boder Deceased E, Sedgewick RP, Gatti RA
    Handb Clin Neurol 2012;103:307-32.
    PMID 21827897
     
    ATM controls meiotic double-strand-break formation
    Lange J, Pan J, Cole F, Thelen MP, Jasin M, Keeney S
    Nature 2011 Oct 16;479(7372):237-40.
    PMID 22002603
     
    Neuropathology in classical and variant ataxia-telangiectasia
    Verhagen MM, Martin JJ, van Deuren M, Ceuterick-de Groote C, Weemaes CM, Kremer BH, Taylor MA, Willemsen MA, Lammens M
    Neuropathology 2012 Jun;32(3):234-44.
    PMID 22017321
     
    ATM and the molecular pathogenesis of ataxia telangiectasia
    McKinnon PJ
    Annu Rev Pathol 2012;7:303-21.
    PMID 22035194
     
    The ATM protein kinase and cellular redox signaling: beyond the DNA damage response
    Ditch S, Paull TT
    Trends Biochem Sci 2012 Jan;37(1):15-22.
    PMID 22079189
     
    Response of fibroblast cultures from ataxia-telangiectasia patients to oxidative stress
    Yi M, Rosin MP, Anderson CK
    Cancer Lett 1990 Oct 8;54(1-2):43-50.
    PMID 2208088
     
    Mitochondrial dysfunction in ataxia-telangiectasia
    Valentin-Vega YA, Maclean KH, Tait-Mulder J, Milasta S, Steeves M, Dorsey FC, Cleveland JL, Green DR, Kastan MB
    Blood 2012 Feb 9;119(6):1490-500.
    PMID 22144182
     
    New insights into the roles of ATM and DNA-PKcs in the cellular response to oxidative stress
    Chen BP, Li M, Asaithamby A
    Cancer Lett 2012 Dec 31;327(1-2):103-10.
    PMID 22155347
     
    Lack of ataxia telangiectasia mutated kinase induces structural and functional changes in the heart: role in β-adrenergic receptor-stimulated apoptosis
    Foster CR, Zha Q, Daniel LL, Singh M, Singh K
    Exp Physiol 2012 Apr;97(4):506-15.
    PMID 22179422
     
    The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/-/ApoE-/- mice
    Mercer JR, Yu E, Figg N, Cheng KK, Prime TA, Griffin JL, Masoodi M, Vidal-Puig A, Murphy MP, Bennett MR
    Free Radic Biol Med 2012 Mar 1;52(5):841-9.
    PMID 22210379
     
    Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study
    Verhagen MM, Last JI, Hogervorst FB, Smeets DF, Roeleveld N, Verheijen F, Catsman-Berrevoets CE, Wulffraat NM, Cobben JM, Hiel J, Brunt ER, Peeters EA, Gómez Garcia EB, van der Knaap MS, Lincke CR, Laan LA, Tijssen MA, van Rijn MA, Majoor-Krakauer D, Visser M, van ', t Veer LJ, Kleijer WJ, van de Warrenburg BP, Warris A, de Groot IJ, de Groot R, Broeks A, Preijers F, Kremer BH, Weemaes CM, Taylor MA, van Deuren M, Willemsen MA
    Hum Mutat 2012 Mar;33(3):561-71.
    PMID 22213089
     
    Mechanisms of replication fork protection: a safeguard for genome stability
    Errico A, Costanzo V
    Crit Rev Biochem Mol Biol May-Jun 2012;47(3):222-35.
    PMID 22324461
     
    Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites
    Saunders-Pullman R, Raymond D, Stoessl AJ, Hobson D, Nakamura K, Pullman S, Lefton D, Okun MS, Uitti R, Sachdev R, Stanley K, San Luciano M, Hagenah J, Gatti R, Ozelius LJ, Bressman SB
    Neurology 2012 Feb 28;78(9):649-57.
    PMID 22345219
     
    Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies
    Agathangelidis A, Darzentas N, Hadzidimitriou A, Brochet X, Murray F, Yan XJ, Davis Z, van Gastel-Mol EJ, Tresoldi C, Chu CC, Cahill N, Giudicelli V, Tichy B, Pedersen LB, Foroni L, Bonello L, Janus A, Smedby K, Anagnostopoulos A, Merle-Beral H, Laoutaris N, Juliusson G, di Celle PF, Pospisilova S, Jurlander J, Geisler C, Tsaftaris A, Lefranc MP, Langerak AW, Oscier DG, Chiorazzi N, Belessi C, Davi F, Rosenquist R, Ghia P, Stamatopoulos K
    Blood 2012 May 10;119(19):4467-75.
    PMID 22415752
     
    Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53
    Williamson CT, Kubota E, Hamill JD, Klimowicz A, Ye R, Muzik H, Dean M, Tu L, Gilley D, Magliocco AM, McKay BC, Bebb DG, Lees-Miller SP
    EMBO Mol Med 2012 Jun;4(6):515-27.
    PMID 22416035
     
    Functional variations in the ATM gene and susceptibility to differentiated thyroid carcinoma
    Xu L, Morari EC, Wei Q, Sturgis EM, Ward LS
    J Clin Endocrinol Metab 2012 Jun;97(6):1913-21.
    PMID 22438227
     
    Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia
    Li J, Chen J, Ricupero CL, Hart RP, Schwartz MS, Kusnecov A, Herrup K
    Nat Med 2012 May;18(5):783-90.
    PMID 22466704
     
    Pexophagy: the selective degradation of peroxisomes
    Till A, Lakhani R, Burnett SF, Subramani S
    Int J Cell Biol 2012;2012:512721.
    PMID 22536249
     
    A role for ATM in hereditary pancreatic cancer
    Bakker JL, de Winter JP
    Cancer Discov 2012 Jan;2(1):14-5.
    PMID 22585162
     
    ATM mutations in patients with hereditary pancreatic cancer
    Roberts NJ, Jiao Y, Yu J, Kopelovich L, Petersen GM, Bondy ML, Gallinger S, Schwartz AG, Syngal S, Cote ML, Axilbund J, Schulick R, Ali SZ, Eshleman JR, Velculescu VE, Goggins M, Vogelstein B, Papadopoulos N, Hruban RH, Kinzler KW, Klein AP
    Cancer Discov 2012 Jan;2(1):41-6.
    PMID 22585167
     
    A new role for ATM: regulating mitochondrial function and mitophagy
    Valentin-Vega YA, Kastan MB
    Autophagy 2012 May 1;8(5):840-1.
    PMID 22617444
     
    Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95
    Carney EF, Srinivasan V, Moss PA, Taylor AM
    J Immunol 2012 Jul 1;189(1):261-8.
    PMID 22649200
     
    Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor
    Shin JU, Lee CH, Lee KT, Lee JK, Lee KH, Kim KM, Kim KM, Park SM, Rhee JC
    Tumour Biol 2012 Oct;33(5):1645-51.
    PMID 22707287
     
    Sequence analysis of mutations and translocations across breast cancer subtypes
    Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L, Cortes ML, Fernandez-Lopez JC, Peng S, Ardlie KG, Auclair D, Bautista-Piña V, Duke F, Francis J, Jung J, Maffuz-Aziz A, Onofrio RC, Parkin M, Pho NH, Quintanar-Jurado V, Ramos AH, Rebollar-Vega R, Rodriguez-Cuevas S, Romero-Cordoba SL, Schumacher SE, Stransky N, Thompson KM, Uribe-Figueroa L, Baselga J, Beroukhim R, Polyak K, Sgroi DC, Richardson AL, Jimenez-Sanchez G, Lander ES, Gabriel SB, Garraway LA, Golub TR, Melendez-Zajgla J, Toker A, Getz G, Hidalgo-Miranda A, Meyerson M
    Nature 2012 Jun 20;486(7403):405-9.
    PMID 22722202
     
    Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography
    Thompson LH
    Mutat Res Oct-Dec 2012;751(2):158-246.
    PMID 22743550
     
    Playing the end game: DNA double-strand break repair pathway choice
    Chapman JR, Taylor MR, Boulton SJ
    Mol Cell 2012 Aug 24;47(4):497-510.
    PMID 22920291
     
    Ataxia telangiectasia mutated impacts insulin-like growth factor 1 signalling in skeletal muscle
    Ching JK, Luebbert SH, Collins RL, Zhang Z, Marupudi N, Banerjee S, Hurd RD, Ralston L, Fisher JS
    Exp Physiol 2013 Feb;98(2):526-35.
    PMID 22941977
     
    Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity
    Beltran H, Yelensky R, Frampton GM, Park K, Downing SR, MacDonald TY, Jarosz M, Lipson D, Tagawa ST, Nanus DM, Stephens PJ, Mosquera JM, Cronin MT, Rubin MA
    Eur Urol 2013 May;63(5):920-6.
    PMID 22981675
     
    Reducing mitochondrial ROS improves disease-related pathology in a mouse model of ataxia-telangiectasia
    D', Souza AD, Parish IA, Krause DS, Kaech SM, Shadel GS
    Mol Ther 2013 Jan;21(1):42-8.
    PMID 23011031
     
    Whole-genome methylation analysis of benign and malignant colorectal tumours
    Beggs AD, Jones A, El-Bahrawy M, Abulafi M, Hodgson SV, Tomlinson IP
    J Pathol 2013 Apr;229(5):697-704.
    PMID 23096130
     
    Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia
    Worth PF, Srinivasan V, Smith A, Last JI, Wootton LL, Biggs PM, Davies NP, Carney EF, Byrd PJ, Taylor AM
    Mov Disord 2013 Apr;28(4):524-8.
    PMID 23143971
     
    Loss of expression of the double strand break repair protein ATM is associated with worse prognosis in colorectal cancer and loss of Ku70 expression is associated with CIN
    Beggs AD, Domingo E, McGregor M, Presz M, Johnstone E, Midgley R, Kerr D, Oukrif D, Novelli M, Abulafi M, Hodgson SV, Fadhil W, Ilyas M, Tomlinson IP
    Oncotarget 2012 Nov;3(11):1348-55.
    PMID 23154512
     
    Programmed induction of DNA double strand breaks during meiosis: setting up communication between DNA and the chromosome structure
    Borde V, de Massy B
    Curr Opin Genet Dev 2013 Apr;23(2):147-55.
    PMID 23313097
     
    mTOR in aging, metabolism, and cancer
    Cornu M, Albert V, Hall MN
    Curr Opin Genet Dev 2013 Feb;23(1):53-62.
    PMID 23317514
     
    Role of SMG-1-mediated Upf1 phosphorylation in mammalian nonsense-mediated mRNA decay
    Yamashita A
    Genes Cells 2013 Mar;18(3):161-75.
    PMID 23356578
     
    Dermatologic manifestations of ataxia-telangiectasia syndrome
    Greenberger S, Berkun Y, Ben-Zeev B, Levi YB, Barziliai A, Nissenkorn A
    J Am Acad Dermatol 2013 Jun;68(6):932-6.
    PMID 23360865
     
    Mechanisms of programmed DNA lesions and genomic instability in the immune system
    Alt FW, Zhang Y, Meng FL, Guo C, Schwer B
    Cell 2013 Jan 31;152(3):417-29.
    PMID 23374339
     
    Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions
    Ambrose M, Gatti RA
    Blood 2013 May 16;121(20):4036-45.
    PMID 23440242
     
    mTOR signaling for biological control and cancer
    Alayev A, Holz MK
    J Cell Physiol 2013 Aug;228(8):1658-64.
    PMID 23460185
     
    The ATM protein kinase: regulating the cellular response to genotoxic stress, and more
    Shiloh Y, Ziv Y
    Nat Rev Mol Cell Biol 2013 Apr;14(4):197-210.
    PMID 23486281
     
    ATM deficiency results in accumulation of DNA-topoisomerase I covalent intermediates in neural cells
    Alagoz M, Chiang SC, Sharma A, El-Khamisy SF
    PLoS One 2013 Apr 23;8(4):e58239.
    PMID 23626666
     
    Variant ataxia telangiectasia: clinical and molecular findings and evaluation of radiosensitive phenotypes in a patient and relatives
    Claes K, Depuydt J, Taylor AM, Last JI, Baert A, Schietecatte P, Vandersickel V, Poppe B, De Leeneer K, D', Hooghe M, Vral A
    Neuromolecular Med 2013 Sep;15(3):447-57.
    PMID 23632773
     
    The role of ATM and DNA damage in neurons: upstream and downstream connections
    Herrup K, Li J, Chen J
    DNA Repair (Amst) 2013 Aug;12(8):600-4.
    PMID 23680599
     
    ATM-dependent DNA damage-response pathway as a determinant in chronic myelogenous leukemia
    Takagi M, Sato M, Piao J, Miyamoto S, Isoda T, Kitagawa M, Honda H, Mizutani S
    DNA Repair (Amst) 2013 Jul;12(7):500-7.
    PMID 23694754
     
    ATM and the epigenetics of the neuronal genome
    Herrup K
    Mech Ageing Dev 2013 Oct;134(10):434-9.
    PMID 23707635
     
    KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling
    Kaidi A, Jackson SP
    Nature 2013 Jun 6;498(7452):70-4.
    PMID 23708966
     
    The repair and signaling responses to DNA double-strand breaks
    Goodarzi AA, Jeggo PA
    Adv Genet 2013;82:1-45.
    PMID 23721719
     
    DNA repair at telomeres: keeping the ends intact
    Webb CJ, Wu Y, Zakian VA
    Cold Spring Harb Perspect Biol 2013 Jun 1;5(6):a012666.
    PMID 23732473
     
    DNA damage response: three levels of DNA repair regulation
    Sirbu BM, Cortez D
    Cold Spring Harb Perspect Biol 2013 Aug 1;5(8):a012724.
    PMID 23813586
     
    ATM signalling and cancer
    Cremona CA, Behrens A
    Oncogene 2014 Jun 26;33(26):3351-60.
    PMID 23851492
     
    Reactive nitrogen species regulate autophagy through ATM-AMPK-TSC2-mediated suppression of mTORC1
    Tripathi DN, Chowdhury R, Trudel LJ, Tee AR, Slack RS, Walker CL, Wogan GN
    Proc Natl Acad Sci U S A 2013 Aug 6;110(32):E2950-7.
    PMID 23878245
     
    Cerebral abnormalities in adults with ataxia-telangiectasia
    Lin DD, Barker PB, Lederman HM, Crawford TO
    AJNR Am J Neuroradiol 2014 Jan;35(1):119-23.
    PMID 23886747
     
    Chromosome instability and oxidative stress markers in patients with ataxia telangiectasia and their parents
    Ludwig LB, Valiati VH, Palazzo RP, Jardim LB, da Rosa DP, Bona S, Rodrigues G, Marroni NP, Prá D, Maluf SW
    Biomed Res Int 2013;2013:762048.
    PMID 23936845
     
    Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks
    Gobbini E, Cesena D, Galbiati A, Lockhart A, Longhese MP
    DNA Repair (Amst) 2013 Oct;12(10):791-9.
    PMID 23953933
     
    A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS
    Zhang J, Kim J, Alexander A, Cai S, Tripathi DN, Dere R, Tee AR, Tait-Mulder J, Di Nardo A, Han JM, Kwiatkowski E, Dunlop EA, Dodd KM, Folkerth RD, Faust PL, Kastan MB, Sahin M, Walker CL
    Nat Cell Biol 2013 Oct;15(10):1186-96.
    PMID 23955302
     
    DNA damage response-related proteins in gastric cancer: ATM, Chk2 and p53 expression and their prognostic value
    Lee HE, Han N, Kim MA, Lee HS, Yang HK, Lee BL, Kim WH
    Pathobiology 2014;81(1):25-35.
    PMID 23969480
     
    Push back to respond better: regulatory inhibition of the DNA double-strand break response
    Panier S, Durocher D
    Nat Rev Mol Cell Biol 2013 Oct;14(10):661-72.
    PMID 24002223
     
    DNA damage sensing by the ATM and ATR kinases
    Maréchal A, Zou L
    Cold Spring Harb Perspect Biol 2013 Sep 1;5(9):a012716.
    PMID 24003211
     
    Effects of ataxia telangiectasia mutated (ATM) genotypes and smoking habits on lung cancer risk in Taiwan
    Hsia TC, Tsai CW, Liang SJ, Chang WS, Lin LY, Chen WC, Tu CY, Tsai CH, Bau DT
    Anticancer Res 2013 Sep;33(9):4067-71.
    PMID 24023351
     
    Repair of strand breaks by homologous recombination
    Jasin M, Rothstein R
    Cold Spring Harb Perspect Biol 2013 Nov 1;5(11):a012740.
    PMID 24097900
     
    Ataxia-telangiectasia: an overview
    Boder E
    Kroc Found Ser 1985;19:1-63.
    PMID 2415689
     
    EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia
    Li J, Hart RP, Mallimo EM, Swerdel MR, Kusnecov AW, Herrup K
    Nat Neurosci 2013 Dec;16(12):1745-53.
    PMID 24162653
     
    Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas
    Pennington KP, Walsh T, Harrell MI, Lee MK, Pennil CC, Rendi MH, Thornton A, Norquist BM, Casadei S, Nord AS, Agnew KJ, Pritchard CC, Scroggins S, Garcia RL, King MC, Swisher EM
    Clin Cancer Res 2014 Feb 1;20(3):764-75.
    PMID 24240112
     
    Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia
    Sharma NK, Lebedeva M, Thomas T, Kovalenko OA, Stumpf JD, Shadel GS, Santos JH
    DNA Repair (Amst) 2014 Jan;13:22-31.
    PMID 24342190
     
    Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling following myocardial infarction: involvement in fibrosis and apoptosis
    Foster CR, Daniel LL, Daniels CR, Dalal S, Singh M, Singh K
    PLoS One 2013 Dec 16;8(12):e83513.
    PMID 24358288
     
    Familial pancreatic cancer: genetic advances
    Rustgi AK
    Genes Dev 2014 Jan 1;28(1):1-7.
    PMID 24395243
     
    Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas
    Palomero T, Couronné L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, Carpenter Z, Abate F, Allegretta M, Haydu JE, Jiang X, Lossos IS, Nicolas C, Balbin M, Bastard C, Bhagat G, Piris MA, Campo E, Bernard OA, Rabadan R, Ferrando AA
    Nat Genet 2014 Feb;46(2):166-70.
    PMID 24413734
     
    Having pancreatic cancer with tumoral loss of ATM and normal TP53 protein expression is associated with a poorer prognosis
    Kim H, Saka B, Knight S, Borges M, Childs E, Klein A, Wolfgang C, Herman J, Adsay VN, Hruban RH, Goggins M
    Clin Cancer Res 2014 Apr 1;20(7):1865-72.
    PMID 24486587
     
    MicroRNA-181a functions as an oncomir in gastric cancer by targeting the tumour suppressor gene ATM
    Zhang X, Nie Y, Li X, Wu G, Huang Q, Cao J, Du Y, Li J, Deng R, Huang D, Chen B, Li S, Wei B
    Pathol Oncol Res 2014 Apr;20(2):381-9.
    PMID 24531888
     
    Non-homologous end joining: emerging themes and unanswered questions
    Radhakrishnan SK, Jette N, Lees-Miller SP
    DNA Repair (Amst) 2014 May;17:2-8.
    PMID 24582502
     
    DNA double-strand break repair in a cellular context
    Shibata A, Jeggo PA
    Clin Oncol (R Coll Radiol) 2014 May;26(5):243-9.
    PMID 24630811
     
    DNA-PK: a dynamic enzyme in a versatile DSB repair pathway
    Davis AJ, Chen BP, Chen DJ
    DNA Repair (Amst) 2014 May;17:21-9.
    PMID 24680878
     
    Base excision repair: a critical player in many games
    Wallace SS
    DNA Repair (Amst) 2014 Jul;19:14-26.
    PMID 24780558
     
    Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes
    Katyal S, Lee Y, Nitiss KC, Downing SM, Li Y, Shimada M, Zhao J, Russell HR, Petrini JH, Nitiss JL, McKinnon PJ
    Nat Neurosci 2014 Jun;17(6):813-21.
    PMID 24793032
     
    Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia
    Kiel MJ, Velusamy T, Rolland D, Sahasrabuddhe AA, Chung F, Bailey NG, Schrader A, Li B, Li JZ, Ozel AB, Betz BL, Miranda RN, Medeiros LJ, Zhao L, Herling M, Lim MS, Elenitoba-Johnson KS
    Blood 2014 Aug 28;124(9):1460-72.
    PMID 24825865
     
    ROS function in redox signaling and oxidative stress
    Schieber M, Chandel NS
    Curr Biol 2014 May 19;24(10):R453-62.
    PMID 24845678
     
    Direct activation of ATM by resveratrol under oxidizing conditions
    Lee JH, Guo Z, Myler LR, Zheng S, Paull TT
    PLoS One 2014 Jun 16;9(6):e97969.
    PMID 24933654
     
    ATM regulates insulin-like growth factor 1-secretory clusterin (IGF-1-sCLU) expression that protects cells against senescence
    Luo X, Suzuki M, Ghandhi SA, Amundson SA, Boothman DA
    PLoS One 2014 Jun 17;9(6):e99983.
    PMID 24937130
     
    Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma
    Rendleman J, Antipin Y, Reva B, Adaniel C, Przybylo JA, Dutra-Clarke A, Hansen N, Heguy A, Huberman K, Borsu L, Paltiel O, Ben-Yehuda D, Brown JR, Freedman AS, Sander C, Zelenetz A, Klein RJ, Shao Y, Lacher M, Vijai J, Offit K, Kirchhoff T
    PLoS One 2014 Jul 10;9(7):e101685.
    PMID 25010664
     
    Ataxia telangiectasia: more variation at clinical and cellular levels
    Taylor AM, Lam Z, Last JI, Byrd PJ
    Clin Genet 2015 Mar;87(3):199-208.
    PMID 25040471
     
    Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia
    Voss S, Pietzner J, Hoche F, Taylor AM, Last JI, Schubert R, Zielen S
    Growth Factors 2014 Jun;32(3-4):123-9.
    PMID 25060036
     
    Hypersensitivity to cell killing and faulty repair of 1-beta-D-arabinofuranosylcytosine-detectable sites in human (ataxia-telangiectasia) fibroblasts treated with 4-nitroquinoline 1-oxide
    Mirzayans R, Smith BP, Paterson MC
    Cancer Res 1989 Oct 15;49(20):5523-9.
    PMID 2507129
     
    A-TWinnipeg: Pathogenesis of rare ATM missense mutation c.6200C>A with decreased protein expression and downstream signaling, early-onset dystonia, cancer, and life-threatening radiotoxicity
    Nakamura K, Fike F, Haghayegh S, Saunders-Pullman R, Dawson AJ, Dörk T, Gatti RA
    Mol Genet Genomic Med 2014 Jul;2(4):332-40.
    PMID 25077176
     
    The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia
    Méneret A, Ahmar-Beaugendre Y, Rieunier G, Mahlaoui N, Gaymard B, Apartis E, Tranchant C, Rivaud-Péchoux S, Degos B, Benyahia B, Suarez F, Maisonobe T, Koenig M, Durr A, Stern MH, Dubois d', Enghien C, Fischer A, Vidailhet M, Stoppa-Lyonnet D, Grabli D, Anheim M
    Neurology 2014 Sep 16;83(12):1087-95.
    PMID 25122203
     
    Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory
    Mehdipour P, Karami F, Javan F, Mehrazin M
    Mol Neurobiol 2015 Aug;52(1):293-302.
    PMID 25159481
     
    Single nucleotide polymorphisms of ataxia telangiectasia mutated and the risk of papillary thyroid carcinoma
    Song CM, Kwon TK, Park BL, Ji YB, Tae K
    Environ Mol Mutagen 2015 Jan;56(1):70-6.
    PMID 25196645
     
    ATM: expanding roles as a chief guardian of genome stability
    Shiloh Y
    Exp Cell Res 2014 Nov 15;329(1):154-61.
    PMID 25218947
     
    The role of double-strand break repair pathways at functional and dysfunctional telomeres
    Doksani Y, de Lange T
    Cold Spring Harb Perspect Biol 2014 Sep 16;6(12):a016576.
    PMID 25228584
     
    T-cell prolymphocytic leukemia frequently shows cutaneous involvement and is associated with gains of MYC, loss of ATM, and TCL1A rearrangement
    Hsi AC, Robirds DH, Luo J, Kreisel FH, Frater JL, Nguyen TT
    Am J Surg Pathol 2014 Nov;38(11):1468-83.
    PMID 25310835
     
    Association of ATM Gene Polymorphism with PTC Metastasis in Female Patients
    Gu Y, Liu X, Yu Y, Shi J, Ai L, Sun H, Kanu JS, Wang C, Liu Y
    Int J Endocrinol 2014;2014:370825.
    PMID 25386189
     
    PIKKs--the solenoid nest where partners and kinases meet
    Baretić D, Williams RL
    Curr Opin Struct Biol 2014 Dec;29:134-42.
    PMID 25460276
     
    Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer
    Grant RC, Selander I, Connor AA, Selvarajah S, Borgida A, Briollais L, Petersen GM, Lerner-Ellis J, Holter S, Gallinger S
    Gastroenterology 2015 Mar;148(3):556-64.
    PMID 25479140
     
    A comprehensive transcriptional portrait of human cancer cell lines
    Klijn C, Durinck S, Stawiski EW, Haverty PM, Jiang Z, Liu H, Degenhardt J, Mayba O, Gnad F, Liu J, Pau G, Reeder J, Cao Y, Mukhyala K, Selvaraj SK, Yu M, Zynda GJ, Brauer MJ, Wu TD, Gentleman RC, Manning G, Yauch RL, Bourgon R, Stokoe D, Modrusan Z, Neve RM, de Sauvage FJ, Settleman J, Seshagiri S, Zhang Z
    Nat Biotechnol 2015 Mar;33(3):306-12.
    PMID 25485619
     
    Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies
    Suarez F, Mahlaoui N, Canioni D, Andriamanga C, Dubois d', Enghien C, Brousse N, Jais JP, Fischer A, Hermine O, Stoppa-Lyonnet D
    J Clin Oncol 2015 Jan 10;33(2):202-8.
    PMID 25488969
     
    Deficiency of ataxia telangiectasia mutated kinase delays inflammatory response in the heart following myocardial infarction
    Daniel LL, Daniels CR, Harirforoosh S, Foster CR, Singh M, Singh K
    J Am Heart Assoc 2014 Dec;3(6):e001286.
    PMID 25520329
     
    Linear growth and endocrine function in children with ataxia telangiectasia
    Ehlayel M, Soliman A, De Sanctis V
    Indian J Endocrinol Metab 2014 Nov;18(Suppl 1):S93-6.
    PMID 25538885
     
    Effect of single nucleotide polymorphism Rs189037 in ATM gene on risk of lung cancer in Chinese: a case-control study
    Liu J, Wang X, Ren Y, Li X, Zhang X, Zhou B
    PLoS One 2014 Dec 26;9(12):e115845.
    PMID 25541996
     
    The DNA-dependent protein kinase: A multifunctional protein kinase with roles in DNA double strand break repair and mitosis
    Jette N, Lees-Miller SP
    Prog Biophys Mol Biol 2015 Mar;117(2-3):194-205.
    PMID 25550082
     
    The methylation of a panel of genes differentiates low-grade from high-grade gliomas
    Majchrzak-Celińska A, Paluszczak J, Szalata M, Barciszewska AM, Nowak S, Kleszcz R, Sherba A, Baer-Dubowska W
    Tumour Biol 2015 May;36(5):3831-41.
    PMID 25563195
     
    Mechanisms of ATM Activation
    Paull TT
    Annu Rev Biochem 2015;84:711-38.
    PMID 25580527
     
    Enhanced sensitivity to camptothecin in ataxia-telangiectasia cells and its relationship with the expression of DNA topoisomerase I
    Smith PJ, Makinson TA, Watson JV
    Int J Radiat Biol 1989 Feb;55(2):217-31.
    PMID 2563396
     
    Somatic inactivation of ATM in hematopoietic cells predisposes mice to cyclin D3 dependent T cell acute lymphoblastic leukemia
    Ehrlich LA, Yang-Iott K, DeMicco A, Bassing CH
    Cell Cycle 2015;14(3):388-98.
    PMID 25659036
     
    ATM protein kinase signaling, type 2 diabetes and cardiovascular disease
    Espach Y, Lochner A, Strijdom H, Huisamen B
    Cardiovasc Drugs Ther 2015 Feb;29(1):51-8.
    PMID 25687661
     
    DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity
    Härtlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kröger A, Nilsson JA, Ek T, Weiss S, Gekara NO
    Immunity 2015 Feb 17;42(2):332-343.
    PMID 25692705
     
    ATM prevents DSB formation by coordinating SSB repair and cell cycle progression
    Khoronenkova SV, Dianov GL
    Proc Natl Acad Sci U S A 2015 Mar 31;112(13):3997-4002.
    PMID 25775545
     
    ATM couples replication stress and metabolic reprogramming during cellular senescence
    Aird KM, Worth AJ, Snyder NW, Lee JV, Sivanand S, Liu Q, Blair IA, Wellen KE, Zhang R
    Cell Rep 2015 May 12;11(6):893-901.
    PMID 25937285
     
    miR-181a promotes G1/S transition and cell proliferation in pediatric acute myeloid leukemia by targeting ATM
    Liu X, Liao W, Peng H, Luo X, Luo Z, Jiang H, Xu L
    J Cancer Res Clin Oncol 2016 Jan;142(1):77-87.
    PMID 26113450
     
    Targeting ATM-deficient CLL through interference with DNA repair pathways
    Knittel G, Liedgens P, Reinhardt HC
    Front Genet 2015 Jun 10;6:207.
    PMID 26113859
     
    Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma
    Bhandaru M, Martinka M, McElwee KJ, Rotte A
    PLoS One 2015 Aug 14;10(8):e0134678.
    PMID 26275218
     
    MacroH2A1 and ATM Play Opposing Roles in Paracrine Senescence and the Senescence-Associated Secretory Phenotype
    Chen H, Ruiz PD, McKimpson WM, Novikov L, Kitsis RN, Gamble MJ
    Mol Cell 2015 Sep 3;59(5):719-31.
    PMID 26300260
     
    ATM functions at the peroxisome to induce pexophagy in response to ROS
    Zhang J, Tripathi DN, Jing J, Alexander A, Kim J, Powell RT, Dere R, Tait-Mulder J, Lee JH, Paull TT, Pandita RK, Charaka VK, Pandita TK, Kastan MB, Walker CL
    Nat Cell Biol 2015 Oct;17(10):1259-1269.
    PMID 26344566
     
    ATM deficiency promotes development of murine B-cell lymphomas that resemble diffuse large B-cell lymphoma in humans
    Hathcock KS, Padilla-Nash HM, Camps J, Shin DM, Triner D, Shaffer AL, Maul RW, Steinberg SM, Gearhart PJ, Staudt LM, Morse HC, Ried T, Hodes RJ
    Blood 2015 Nov 12;126(20):2291-301.
    PMID 26400962
     
    The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4
    Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, Lu T, Yankner BA, Campisi J, Elledge SJ
    Science 2015 Sep 25;349(6255):aaa5612.
    PMID 26404840
     
    Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients
    Hu C, Hart SN, Bamlet WR, Moore RM, Nandakumar K, Eckloff BW, Lee YK, Petersen GM, McWilliams RR, Couch FJ
    Cancer Epidemiol Biomarkers Prev 2016 Jan;25(1):207-11.
    PMID 26483394
     
    ATM rs189037 (G > A) polymorphism and risk of lung cancer and head and neck cancer: A meta-analysis
    Bhowmik A, Nath S, Das S, Ghosh SK, Choudhury Y
    Meta Gene 2015 Sep 3;6:42-8.
    PMID 26504743
     
    DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
    Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A', Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS
    N Engl J Med 2015 Oct 29;373(18):1697-708.
    PMID 26510020
     
    Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency
    Jiang D, Zhang Y, Hart RP, Chen J, Herrup K, Li J
    Brain 2015 Dec;138(Pt 12):3520-36.
    PMID 26510954
     
    The current state of eukaryotic DNA base damage and repair
    Bauer NC, Corbett AH, Doetsch PW
    Nucleic Acids Res 2015 Dec 2;43(21):10083-101.
    PMID 26519467
     
    Concurrent Mutations in ATM and Genes Associated with Common γ Chain Signaling in Peripheral T Cell Lymphoma
    Simpson HM, Khan RZ, Song C, Sharma D, Sadashivaiah K, Furusawa A, Liu X, Nagaraj S, Sengamalay N, Sadzewicz L, Tallon LJ, Chen QC, Livak F, Rapoport AP, Kimball A, Banerjee A
    PLoS One 2015 Nov 4;10(11):e0141906.
    PMID 26536348
     
    Complex interactions between the DNA-damage response and mammalian telomeres
    Arnoult N, Karlseder J
    Nat Struct Mol Biol 2015 Nov;22(11):859-66.
    PMID 26581520
     
    Liver Disease in Pediatric Patients With Ataxia Telangiectasia: A Novel Report
    Weiss B, Krauthammer A, Soudack M, Lahad A, Sarouk I, Somech R, Heimer G, Ben-Zeev B, Nissenkorn A
    J Pediatr Gastroenterol Nutr 2016 Apr;62(4):550-5.
    PMID 26594831
     
    ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia
    Bhatt JM, Bush A, van Gerven M, Nissenkorn A, Renke M, Yarlett L, Taylor M, Tonia T, Warris A, Zielen S, Zinna S, Merkus PJ,
    Eur Respir Rev 2015 Dec;24(138):565-81.
    PMID 26621971
     
    Genomic landscape of liposarcoma
    Kanojia D, Nagata Y, Garg M, Lee DH, Sato A, Yoshida K, Sato Y, Sanada M, Mayakonda A, Bartenhagen C, Klein HU, Doan NB, Said JW, Mohith S, Gunasekar S, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Myklebost O, Yang H, Dugas M, Meza-Zepeda LA, Silberman AW, Forscher C, Tyner JW, Ogawa S, Koeffler HP
    Oncotarget 2015 Dec 15;6(40):42429-44.
    PMID 26643872
     
    Mutational analysis of pulmonary tumours with neuroendocrine features using targeted massive parallel sequencing: a comparison of a neglected tumour group
    Vollbrecht C, Werner R, Walter RF, Christoph DC, Heukamp LC, Peifer M, Hirsch B, Burbat L, Mairinger T, Schmid KW, Wohlschlaeger J, Mairinger FD
    Br J Cancer 2015 Dec 22;113(12):1704-11.
    PMID 26645239
     
    Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: a cohort study
    Pommerening H, van Dullemen S, Kieslich M, Schubert R, Zielen S, Voss S
    Orphanet J Rare Dis 2015 Dec 9;10:155.
    PMID 26645295
     
    Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer
    Roberts NJ, Norris AL, Petersen GM, Bondy ML, Brand R, Gallinger S, Kurtz RC, Olson SH, Rustgi AK, Schwartz AG, Stoffel E, Syngal S, Zogopoulos G, Ali SZ, Axilbund J, Chaffee KG, Chen YC, Cote ML, Childs EJ, Douville C, Goes FS, Herman JM, Iacobuzio-Donahue C, Kramer M, Makohon-Moore A, McCombie RW, McMahon KW, Niknafs N, Parla J, Pirooznia M, Potash JB, Rhim AD, Smith AL, Wang Y, Wolfgang CL, Wood LD, Zandi PP, Goggins M, Karchin R, Eshleman JR, Papadopoulos N, Kinzler KW, Vogelstein B, Hruban RH, Klein AP
    Cancer Discov 2016 Feb;6(2):166-75.
    PMID 26658419
     
    Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen
    Kozlov SV, Waardenberg AJ, Engholm-Keller K, Arthur JW, Graham ME, Lavin M
    Mol Cell Proteomics 2016 Mar;15(3):1032-47.
    PMID 26699800
     
    ATM kinase: Much more than a DNA damage responsive protein
    Guleria A, Chandna S
    DNA Repair (Amst) 2016 Mar;39:1-20.
    PMID 26777338
     
    Serum Interleukin-6 Levels and Pulmonary Function in Ataxia-Telangiectasia
    McGrath-Morrow SA, Collaco JM, Detrick B, Lederman HM
    J Pediatr 2016 Apr;171:256-61.e1.
    PMID 26851119
     
    Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort
    Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, Lahad A, Sarouk I, Modan-Moses D
    Pediatr Res 2016 Jun;79(6):889-94.
    PMID 26891003
     
    The peroxisome as a cell signaling organelle
    Tripathi DN, Walker CL
    Curr Opin Cell Biol 2016 Apr;39:109-12.
    PMID 26967755
     
    ATM and ATR signaling at a glance
    Awasthi P, Foiani M, Kumar A
    J Cell Sci 2016 Mar 15;129(6):1285.
    PMID 26979625
     
    Genome instability: Linking ageing and brain degeneration
    Barzilai A, Schumacher B, Shiloh Y
    Mech Ageing Dev 2017 Jan;161(Pt A):4-18.
    PMID 27041231
     
    Structure of the human dimeric ATM kinase
    Lau WC, Li Y, Liu Z, Gao Y, Zhang Q, Huen MS
    Cell Cycle 2016;15(8):1117-24.
    PMID 27097373
     
    Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas
    Ritterhouse LL, Nowak JA, Strickland KC, Garcia EP, Jia Y, Lindeman NI, Macconaill LE, Konstantinopoulos PA, Matulonis UA, Liu J, Berkowitz RS, Nucci MR, Crum CP, Sholl LM, Howitt BE
    Mod Pathol 2016 Aug;29(8):893-903.
    PMID 27150160
     
    Next-Generation Sequencing in Salivary Gland Basal Cell Adenocarcinoma and Basal Cell Adenoma
    Wilson TC, Ma D, Tilak A, Tesdahl B, Robinson RA
    Head Neck Pathol 2016 Dec;10(4):494-500.
    PMID 27224988
     
    Structure of the intact ATM/Tel1 kinase
    Wang X, Chu H, Lv M, Zhang Z, Qiu S, Liu H, Shen X, Wang W, Cai G
    Nat Commun 2016 May 27;7:11655.
    PMID 27229179
     
    Gene mutations and actionable genetic lesions in mantle cell lymphoma
    Ahmed M, Zhang L, Nomie K, Lam L, Wang M
    Oncotarget 2016 Sep 6;7(36):58638-58648.
    PMID 27449094
     
    ATM mutations in major stereotyped subsets of chronic lymphocytic leukemia: enrichment in subset #2 is associated with markedly short telomeres
    Navrkalova V, Young E, Baliakas P, Radova L, Sutton LA, Plevova K, Mansouri L, Ljungström V, Ntoufa S, Davis Z, Juliusson G, Smedby KE, Belessi C, Panagiotidis P, Touloumenidou T, Davi F, Langerak AW, Ghia P, Strefford JC, Oscier D, Mayer J, Stamatopoulos K, Pospisilova S, Rosenquist R, Trbusek M
    Haematologica 2016 Sep;101(9):e369-73.
    PMID 27479817
     
    Biallelic ATM alterations detected at diagnosis identify a subset of treatment-naïve chronic lymphocytic leukemia patients with reduced overall survival similar to patients with p53 deletion
    Lozano-Santos C, García-Vela JA, Pérez-Sanz N, Nova-Gurumeta S, Fernandez-Cuevas B, Gomez-Lozano N, Sánchez-Beato M, Sanchez-Godoy P, Bueno JL, Garcia-Marco JA
    Leuk Lymphoma 2017 Apr;58(4):859-865.
    PMID 27499002
     
    ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2)
    Jiang Y, Chen HC, Su X, Thompson PA, Liu X, Do KA, Wierda W, Keating MJ, Plunkett W
    Blood Cancer J 2016 Sep 2;6(9):e465.
    PMID 27588518
     
    DNA Repair in Prostate Cancer: Biology and Clinical Implications
    Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, Olmos D, Pritchard CC, Rubin MA, de Bono JS
    Eur Urol 2017 Mar;71(3):417-425.
    PMID 27590317
     
    Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility
    Adel Fahmideh M, Lavebratt C, Schüz J, Röösli M, Tynes T, Grotzer MA, Johansen C, Kuehni CE, Lannering B, Prochazka M, Schmidt LS, Feychting M
    Oncotarget 2016 Sep 27;7(39):63640-63650.
    PMID 27613841
     
    Spectrum of mutations in leiomyosarcomas identified by clinical targeted next-generation sequencing
    Lee PJ, Yoo NS, Hagemann IS, Pfeifer JD, Cottrell CE, Abel HJ, Duncavage EJ
    Exp Mol Pathol 2017 Feb;102(1):156-161.
    PMID 28093192
     
    The depletion of ATM inhibits colon cancer proliferation and migration via B56γ2-mediated Chk1/p53/CD44 cascades
    Liu R, Tang J, Ding C, Liang W, Zhang L, Chen T, Xiong Y, Dai X, Li W, Xu Y, Hu J, Lu L, Liao W, Lu X
    Cancer Lett 2017 Apr 1;390:48-57.
    PMID 28093285
     
    Whole-exome sequencing identified mutational profiles of high-grade colon adenomas
    Lee SH, Jung SH, Kim TM, Rhee JK, Park HC, Kim MS, Kim SS, An CH, Lee SH, Chung YJ
    Oncotarget 2017 Jan 24;8(4):6579-6588.
    PMID 28179590
     
    Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis
    Ratnaparkhe M, Hlevnjak M, Kolb T, Jauch A, Maass KK, Devens F, Rode A, Hovestadt V, Korshunov A, Pastorczak A, Mlynarski W, Sungalee S, Korbel J, Hoell J, Fischer U, Milde T, Kramm C, Nathrath M, Chrzanowska K, Tausch E, Takagi M, Taga T, Constantini S, Loeffen J, Meijerink J, Zielen S, Gohring G, Schlegelberger B, Maass E, Siebert R, Kunz J, Kulozik AE, Worst B, Jones DT, Pfister SM, Zapatka M, Lichter P, Ernst A
    Leukemia 2017 Oct;31(10):2048-2056.
    PMID 28196983
     
    The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study
    Chen S, Zhang JQ, Chen JZ, Chen HX, Qiu FN, Yan ML, Chen YL, Peng CH, Tian YF, Wang YD
    Int J Biol Macromol 2017 Sep;102:718-728.
    PMID 28344092
     
    Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC
    Petersen LF, Klimowicz AC, Otsuka S, Elegbede AA, Petrillo SK, Williamson T, Williamson CT, Konno M, Lees-Miller SP, Hao D, Morris D, Magliocco AM, Bebb DG
    Oncotarget 2017 Jun 13;8(24):38326-38336.
    PMID 28418844
     
    ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy
    Antonelli M, Strappazzon F, Arisi I, Brandi R, D', Onofrio M, Sambucci M, Manic G, Vitale I, Barilà D, Stagni V
    Oncotarget 2017 Mar 28;8(13):21692-21709.
    PMID 28423511
     
    Susceptibility of ATM-deficient pancreatic cancer cells to radiation
    Ayars M, Eshleman J, Goggins M
    Cell Cycle 2017 May 19;16(10):991-998.
    PMID 28453388
     
    Structures of closed and open conformations of dimeric human ATM
    Baretić D, Pollard HK, Fisher DI, Johnson CM, Santhanam B, Truman CM, Kouba T, Fersht AR, Phillips C, Williams RL
    Sci Adv 2017 May 10;3(5):e1700933.
    PMID 28508083
     
    Silencing of ATM expression by siRNA technique contributes to glioma stem cell radiosensitivity in vitro and in vivo
    Li Y, Li L, Wu Z, Wang L, Wu Y, Li D, Ma U, Shao J, Yu H, Wang D
    Oncol Rep 2017 Jul;38(1):325-335.
    PMID 28560406
     
    ATM, radiation, and the risk of second primary breast cancer
    Bernstein JL, , Concannon P
    Int J Radiat Biol 2017 Oct;93(10):1121-1127.
    PMID 28627265
     
    Rare germline variants in ATM are associated with chronic lymphocytic leukemia
    Tiao G, Improgo MR, Kasar S, Poh W, Kamburov A, Landau DA, Tausch E, Taylor-Weiner A, Cibulskis C, Bahl S, Fernandes SM, Hoang K, Rheinbay E, Kim HT, Bahlo J, Robrecht S, Fischer K, Hallek M, Gabriel S, Lander ES, Stilgenbauer S, Wu CJ, Kiezun A, Getz G, Brown JR
    Leukemia 2017 Oct;31(10):2244-2247.
    PMID 28652578
     
    Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks
    Decker B, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Ahmed S, Baynes C, Conroy DM, Brown J, Luben R, Ostrander EA, Pharoah PD, Dunning AM, Easton DF
    J Med Genet 2017 Nov;54(11):732-741.
    PMID 28779002
     
    The role of the ataxia telangiectasia mutated gene in lung cancer: recent advances in research
    Xu Y, Gao P, Lv X, Zhang L, Zhang J
    Ther Adv Respir Dis 2017 Sep;11(9):375-380.
    PMID 28825373
     
    Identifying actionable variants using next generation sequencing in patients with a historical diagnosis of undifferentiated pleomorphic sarcoma
    Lewin J, Garg S, Lau BY, Dickson BC, Traub F, Gokgoz N, Griffin AM, Ferguson PC, Andrulis IL, Sim HW, Kamel-Reid S, Stockley TL, Siu LL, Wunder JS, Razak ARA
    Int J Cancer 2018 Jan 1;142(1):57-65.
    PMID 28891048
     
    ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer
    Drosos Y, Escobar D, Chiang MY, Roys K, Valentine V, Valentine MB, Rehg JE, Sahai V, Begley LA, Ye J, Paul L, McKinnon PJ, Sosa-Pineda B
    Sci Rep 2017 Sep 11;7(1):11144.
    PMID 28894253
     
    Patients with chronic lymphocytic leukemia and complex karyotype show an adverse outcome even in absence of TP53/ATM FISH deletions
    Puiggros A, Collado R, Calasanz MJ, Ortega M, Ruiz-Xivillé N, Rivas-Delgado A, Luño E, González T, Navarro B, García-Malo M, Valiente A, Hernández JÁ, Ardanaz MT, Piñan MÁ, Blanco ML, Hernández-Sánchez M, Batlle-López A, Salgado R, Salido M, Ferrer A, Abrisqueta P, Gimeno E, Abella E, Ferrá C, Terol MJ, Ortuño F, Costa D, Moreno C, Carbonell F, Bosch F, Delgado J, Espinet B
    Oncotarget 2017 Apr 21;8(33):54297-54303.
    PMID 28903342
     
    Association between ATM gene polymorphisms, lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis
    Yan Z, Tong X, Ma Y, Liu S, Yang L, Yang X, Yang X, Bai M, Fan H
    BMC Pulm Med 2017 Dec 15;17(1):205.
    PMID 29246212
     
    Lymphocyte subpopulations in ataxia-telangiectasia
    Weaver M, Gatti RA
    Kroc Found Ser 1985;19:309-14.
    PMID 2933491
     
    Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer
    Hirasawa A, Imoto I, Naruto T, Akahane T, Yamagami W, Nomura H, Masuda K, Susumu N, Tsuda H, Aoki D
    Oncotarget 2017 Nov 28;8(68):112258-112267.
    PMID 29348823
     
    Mutation analysis of adenomas and carcinomas of the colon: Early and late drivers
    Wolff RK, Hoffman MD, Wolff EC, Herrick JS, Sakoda LC, Samowitz WS, Slattery ML
    Genes Chromosomes Cancer 2018 Jul;57(7):366-376.
    PMID 29575536
     
    Germline genetic variants in somatically significantly mutated genes in tumors are associated with renal cell carcinoma risk and outcome
    Shu X, Gu J, Huang M, Tannir NM, Matin SF, Karam JA, Wood CG, Wu X, Ye Y
    Carcinogenesis 2018 May 28;39(6):752-757.
    PMID 29635281
     
    Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers
    Renault AL, Mebirouk N, Fuhrmann L, Bataillon G, Cavaciuti E, Le Gal D, Girard E, Popova T, La Rosa P, Beauvallet J, Eon-Marchais S, Dondon MG, d', Enghien CD, Laugé A, Chemlali W, Raynal V, Labbé M, Bièche I, Baulande S, Bay JO, Berthet P, Caron O, Buecher B, Faivre L, Fresnay M, Gauthier-Villars M, Gesta P, Janin N, Lejeune S, Maugard C, Moutton S, Venat-Bouvet L, Zattara H, Fricker JP, Gladieff L, Coupier I, , , , Chenevix-Trench G, Hall J, Vincent-Salomon A, Stoppa-Lyonnet D, Andrieu N, Lesueur F
    Breast Cancer Res 2018 Apr 17;20(1):28.
    PMID 29665859
     
    ATM/RB1 mutations predict shorter overall survival in urothelial cancer
    Yin M, Grivas P, Emamekhoo H, Mendiratta P, Ali S, Hsu J, Vasekar M, Drabick JJ, Pal S, Joshi M
    Oncotarget 2018 Mar 30;9(24):16891-16898.
    PMID 29682192
     
    Breakage of the T cell receptor alpha chain locus in non malignant clones from patients with ataxia telangiectasia
    Heppell A, Butterworth SV, Hollis RJ, Kennaugh AA, Beatty DW, Taylor AM
    Hum Genet 1988 Aug;79(4):360-4.
    PMID 2970426
     
    Ataxia-Telangiectasia-Mutated Protein Expression as a Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands
    Bazarsad S, Kim JY, Zhang X, Kim KY, Lee DY, Ryu MH, Kim J
    Yonsei Med J 2018 Aug;59(6):717-726.
    PMID 29978608
     
    ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients
    Mareckova A, Malcikova J, Tom N, Pal K, Radova L, Salek D, Janikova A, Moulis M, Smardova J, Kren L, Mayer J, Trbusek M
    Leuk Lymphoma 2019 Jun;60(6):1420-1428.
    PMID 30626249
     
    A review on role of ATM gene in hereditary transfer of colorectal cancer
    Sriramulu S, Ramachandran M, Subramanian S, Kannan R, Gopinath M, Sollano J, Bissi L, Banerjee A, Marotta F, Pathak S
    Acta Biomed 2019 Jan 15;89(4):463-469.
    PMID 30657113
     
    ATM rs189037 (G > A) polymorphism increased the risk of cancer: an updated meta-analysis
    Zhao ZL, Xia L, Zhao C, Yao J
    BMC Med Genet 2019 Feb 1;20(1):28.
    PMID 30709340
     
    A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion
    Yin S, Gambe RG, Sun J, Martinez AZ, Cartun ZJ, Regis FFD, Wan Y, Fan J, Brooks AN, Herman SEM, Ten Hacken E, Taylor-Weiner A, Rassenti LZ, Ghia EM, Kipps TJ, Obeng EA, Cibulskis CL, Neuberg D, Campagna DR, Fleming MD, Ebert BL, Wiestner A, Leshchiner I, DeCaprio JA, Getz G, Reed R, Carrasco RD, Wu CJ, Wang L
    Cancer Cell 2019 Feb 11;35(2):283-296.e5.
    PMID 30712845
     
    Prevalence of Germline Variants in Prostate Cancer and Implications for Current Genetic Testing Guidelines
    Nicolosi P, Ledet E, Yang S, Michalski S, Freschi B, O', Leary E, Esplin ED, Nussbaum RL, Sartor O
    JAMA Oncol 2019 Apr 1;5(4):523-528.
    PMID 30730552
     
    Low Expression of ATM Indicates a Poor Prognosis in Clear Cell Renal Cell Carcinoma
    Ren W, Xue B, Chen M, Liu L, Zu X
    Clin Genitourin Cancer 2019 Jun;17(3):e433-e439.
    PMID 30773312
     
    Identification of Rare Variants Predisposing to Thyroid Cancer
    Wang Y, Liyanarachchi S, Miller KE, Nieminen TT, Comiskey DF, Li W, Brock P, Symer DE, Akagi K, DeLap KE, He H, Koboldt DC, de la Chapelle A
    Thyroid 2019 Jul;29(7):946-955.
    PMID 30957677
     
    Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway
    Shen M, Xu Z, Xu W, Jiang K, Zhang F, Ding Q, Xu Z, Chen Y
    J Exp Clin Cancer Res 2019 Apr 8;38(1):149.
    PMID 30961670
     
    Alterations in DNA Damage Repair Genes in Primary Liver Cancer
    Lin J, Shi J, Guo H, Yang X, Jiang Y, Long J, Bai Y, Wang D, Yang X, Wan X, Zhang L, Pan J, Hu K, Guan M, Huo L, Sang X, Wang K, Zhao H
    Clin Cancer Res 2019 Aug 1;25(15):4701-4711.
    PMID 31068370
     
    Germline and Somatic Mutations in Prostate Cancer for the Clinician
    Cheng HH, Sokolova AO, Schaeffer EM, Small EJ, Higano CS
    J Natl Compr Canc Netw 2019 May 1;17(5):515-521.
    PMID 31085765
     
    ATM rs189037 significantly increases the risk of cancer in non-smokers rather than smokers: an updated meta-analysis
    He X, Wang P, Li Y, Shen N
    Biosci Rep 2019 Jun 28;39(6):BSR20191298.
    PMID 31201228
     
    Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR
    Baretic D, Maia de Oliveira T, Niess M, Wan P, Pollard H, Johnson CM, Truman C, McCall E, Fisher D, Williams R, Phillips C
    Prog Biophys Mol Biol 2019 Oct;147:4-16.
    PMID 31255703
     
    Prognostic relevance of ATM protein in uveal melanoma and its association with clinicopathological factors
    Jha J, Singh MK, Singh L, Pushker N, Bajaj MS, Sen S, Kashyap S
    Int J Clin Oncol 2019 Dec;24(12):1526-1535.
    PMID 31377937
     
    Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and Mortality in Patients With Non-Small Cell Lung Cancer
    Chen Y, Chen G, Li J, Huang YY, Li Y, Lin J, Chen LZ, Lu JP, Wang YQ, Wang CX, Pan LK, Xia XF, Yi X, Chen CB, Zheng XW, Guo ZQ, Pan JJ
    JAMA Netw Open 2019 Sep 4;2(9):e1911895.
    PMID 31539077
     
    ATM Dysfunction in Pancreatic Adenocarcinoma and Associated Therapeutic Implications
    Armstrong SA, Schultz CW, Azimi-Sadjadi A, Brody JR, Pishvaian MJ
    Mol Cancer Ther 2019 Nov;18(11):1899-1908.
    PMID 31676541
     
    EZH2 Loss Drives Resistance to Carboplatin and Paclitaxel in Serous Ovarian Cancers Expressing ATM
    Naskou J, Beiter Y, van Rensburg R, Honisch E, Rudelius M, Schlensog M, Gottstein J, Walter L, Braicu EI, Sehouli J, Darb-Esfahani S, Staebler A, Hartkopf AD, Brucker S, Wallwiener D, Beyer I, Niederacher D, Fehm T, Templin MF, Neubauer H
    Mol Cancer Res 2020 Feb;18(2):278-286.
    PMID 31704732
     
    Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients
    Sugino K, Tamura R, Nakaoka H, Yachida N, Yamaguchi M, Mori Y, Yamawaki K, Suda K, Ishiguro T, Adachi S, Isobe M, Yamaguchi M, Kashima K, Motoyama T, Inoue I, Yoshihara K, Enomoto T
    Sci Rep 2019 Nov 28;9(1):17808.
    PMID 31780705
     
    Hereditary prostate cancer - Primetime for genetic testing?
    Heidegger I, Tsaur I, Borgmann H, Surcel C, Kretschmer A, Mathieu R, Visschere P, Valerio M, van den Bergh RCN, Ost P, Tilki D, Gandaglia G, Ploussard G,
    Cancer Treat Rev 2019 Dec;81:101927.
    PMID 31783313
     
    MiR-100 regulates cell viability and apoptosis by targeting ATM in pediatric acute myeloid leukemia
    Sun Y, Wang H, Luo C
    Biochem Biophys Res Commun 2020 Feb 19;522(4):855-861.
    PMID 31801665
     
    Prevalence of pathogenic germline cancer risk variants in high-risk urothelial carcinoma
    Nassar AH, Abou Alaiwi S, AlDubayan SH, Moore N, Mouw KW, Kwiatkowski DJ, Choueiri TK, Curran C, Berchuck JE, Harshman LC, Nuzzo PV, Chanza NM, Van Allen E, Esplin ED, Yang S, Callis T, Garber JE, Rana HQ, Sonpavde G
    Genet Med 2020 Apr;22(4):709-718.
    PMID 31844177
     
    Mutation Status and Epithelial Differentiation Stratify Recurrence Risk in Chordoid Meningioma-A Multicenter Study with High Prognostic Relevance
    Georgescu MM, Nanda A, Li Y, Mobley BC, Faust PL, Raisanen JM, Olar A
    Cancers (Basel) 2020 Jan 17;12(1):225.
    PMID 31963394
     
    ATM Serine/Threonine Kinase and its Role in Pancreatic Risk
    Nanda N, Roberts NJ
    Genes (Basel) 2020 Jan 17;11(1):108.
    PMID 31963441
     
    Methylation of the ataxia telangiectasia mutated gene (ATM) promoter as a radiotherapy outcome biomarker in patients with hepatocellular carcinoma
    Yan X, Wu T, Tang M, Chen D, Huang M, Zhou S, Zhang H, Yang X, Li G
    Medicine (Baltimore) 2020 Jan;99(4):e18823.
    PMID 31977876
     
    Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia
    Mobark NA, Alharbi M, Alhabeeb L, AlMubarak L, Alaljelaify R, AlSaeed M, Almutairi A, Alqubaishi F, Ahmad M, Al-Banyan A, Alotabi FE, Barakeh D, AlZahrani M, Al-Khalidi H, Ajlan A, Ramkissoon LA, Ramkissoon SH, Abedalthagafi M
    PLoS One 2020 Jan 29;15(1):e0228356.
    PMID 31995621
     
    Localization of an ataxia-telangiectasia gene to chromosome 11q22-23
    Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NG, Lange K
    Nature 1988 Dec 8;336(6199):577-80.
    PMID 3200306
     
    Germline alterations in patients with biliary tract cancers: A spectrum of significant and previously underappreciated findings
    Maynard H, Stadler ZK, Berger MF, Solit DB, Ly M, Lowery MA, Mandelker D, Zhang L, Jordan E, El Dika I, Kemel Y, Ladanyi M, Robson ME, O', Reilly EM, Abou-Alfa GK
    Cancer 2020 Jan 1;126(9):1995-2002.
    PMID 32012241
     
    Clinical significance of TP53, BIRC3, ATM and MAPK-ERK genes in chronic lymphocytic leukaemia: data from the randomised UK LRF CLL4 trial
    Blakemore SJ, Clifford R, Parker H, Antoniou P, Stec-Dziedzic E, Larrayoz M, Davis Z, Kadalyayil L, Colins A, Robbe P, Vavoulis D, Forster J, Carr L, Morilla R, Else M, Bryant D, McCarthy H, Walewska RJ, Steele AJ, Chan J, Speight G, Stankovic T, Cragg MS, Catovsky D, Oscier DG, Rose-Zerilli MJJ, Schuh A, Strefford JC
    Leukemia 2020 Jul;34(7):1760-1774.
    PMID 32015491
     
    Familial Pancreatic Cancer: Current Perspectives
    Llach J, Carballal S, Moreira L
    Cancer Manag Res 2020 Jan 31;12:743-758.
    PMID 32099470
     
    The ATM rs189037 G>A polymorphism is associated with the risk and prognosis of gastric cancer in Chinese individuals: A case-control study
    Tao Y, Mei Y, Ying R, Chen S, Wei Z
    Gene 2020 May 30;741:144578.
    PMID 32171823
     
    ATM-Deficient Cancers Provide New Opportunities for Precision Oncology
    Jette NR, Kumar M, Radhamani S, Arthur G, Goutam S, Yip S, Kolinsky M, Williams GJ, Bose P, Lees-Miller SP
    Cancers (Basel) 2020 Mar 14;12(3):687.
    PMID 32183301
     
    Abnormal expression of p-ATM/CHK2 in nasal extranodal NK/T cell lymphoma, nasal type, is correlated with poor prognosis
    Ye Q, Chen H, Wen Z, Guo W, Huang Y, Mo X
    J Clin Pathol 2021 Apr;74(4):223-227.
    PMID 32220941
     
    ATM gene polymorphisms are associated with poor prognosis of non-small cell lung cancer receiving radiation therapy
    Mou J, Hu T, Wang Z, Chen W, Wang Y, Zhang W
    Aging (Albany NY) 2020 Apr 24;12(8):7465-7479.
    PMID 32329754
     
    DNA damage repair pathway alterations in metastatic clear cell renal cell carcinoma and implications on systemic therapy
    Ged Y, Chaim JL, DiNatale RG, Knezevic A, Kotecha RR, Carlo MI, Lee CH, Foster A, Feldman DR, Teo MY, Iyer G, Chan T, Patil S, Motzer RJ, Hakimi AA, Voss MH
    J Immunother Cancer 2020 Jun;8(1):e000230.
    PMID 32571992
     
    Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis
    Hill HA, Qi X, Jain P, Nomie K, Wang Y, Zhou S, Wang ML
    Blood Adv 2020 Jul 14;4(13):2927-2938.
    PMID 32598477
     
    Resveratrol activates DNA damage response through inhibition of polo-like kinase 1 (PLK1) in natural killer/T cell lymphoma
    Sui X, Zhang C, Jiang Y, Zhou J, Xu C, Tang F, Chen B, Xu H, Wang S, Wang X
    Ann Transl Med 2020 Jun;8(11):688.
    PMID 32617308
     
    Hereditary Predisposition to Prostate Cancer: From Genetics to Clinical Implications
    Brandão A, Paulo P, Teixeira MR
    Int J Mol Sci 2020 Jul 16;21(14):5036.
    PMID 32708810
     
    ATM mutations improve radio-sensitivity in wild-type isocitrate dehydrogenase-associated high-grade glioma: retrospective analysis using next-generation sequencing data
    Kim N, Kim SH, Kang SG, Moon JH, Cho J, Suh CO, In Yoon H, Chang JH
    Radiat Oncol 2020 Jul 31;15(1):184.
    PMID 32736562
     
    ATM Mutations Benefit Bladder Cancer Patients Treated With Immune Checkpoint Inhibitors by Acting on the Tumor Immune Microenvironment
    Yi R, Lin A, Cao M, Xu A, Luo P, Zhang J
    Front Genet 2020 Aug 14;11:933.
    PMID 32922441
     
    Characteristics of cancer susceptibility genes mutations in 282 patients with gastric adenocarcinoma
    Ji K, Ao S, He L, Zhang L, Feng L, Lyu G
    Chin J Cancer Res 2020 Aug;32(4):508-515.
    PMID 32963463
     
    PARP Inhibitors in Metastatic Prostate Cancer: Evidence to Date
    Nizialek E, Antonarakis ES
    Cancer Manag Res 2020 Sep 7;12:8105-8114.
    PMID 32982407
     
    ATM inhibition synergizes with fenofibrate in high grade serous ovarian cancer cells
    Chen CW, Buj R, Dahl ES, Leon KE, Aird KM
    Heliyon 2020 Sep 29;6(9):e05097.
    PMID 33024871
     
    Poly(ADP-Ribose) Polymerase Inhibitors in Prostate Cancer: Molecular Mechanisms, and Preclinical and Clinical Data
    Sigorski D, Iżycka-Świeszewska E, Bodnar L
    Target Oncol 2020 Dec;15(6):709-722.
    PMID 33044685
     
    Alterations of DNA damage response genes correlate with response and overall survival in anti-PD-1/PD-L1-treated advanced urothelial cancer
    Joshi M, Grivas P, Mortazavi A, Monk P, Clinton SK, Sue-Ann Woo M, Holder SL, Drabick JJ, Yin M
    Cancer Med 2020 Dec;9(24):9365-9372.
    PMID 33098265
     
    Targeting DNA Damage Response in Prostate and Breast Cancer
    Wengner AM, Scholz A, Haendler B
    Int J Mol Sci 2020 Nov 4;21(21):8273.
    PMID 33158305
     
    Genetic Mutations and Variants in the Susceptibility of Familial Non-Medullary Thyroid Cancer
    Miasaki FY, Fuziwara CS, Carvalho GA, Kimura ET
    Genes (Basel) 2020 Nov 18;11(11):1364.
    PMID 33218058
     
    The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer
    Fan Y, Ying H, Wu X, Chen H, Hu Y, Zhang H, Wu L, Yang Y, Mao B, Zheng L
    Cancer Biol Med 2020 Nov 15;17(4):1002-1013.
    PMID 33299649
     
    A reduced panel of eight genes (ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53) as an estimator of the tumor mutational burden in chronic lymphocytic leukemia
    Chauzeix J, Pastoret C, Donaty L, Gachard N, Fest T, Feuillard J, Rizzo D
    Int J Lab Hematol 2020 Dec 16.
    PMID 33325634
     
    Genomic profiling reveals high frequency of DNA repair genetic aberrations in gallbladder cancer
    Abdel-Wahab R, Yap TA, Madison R, Pant S, Cooke M, Wang K, Zhao H, Bekaii-Saab T, Karatas E, Kwong LN, Meric-Bernstam F, Borad M, Javle M
    Sci Rep 2020 Dec 16;10(1):22087.
    PMID 33328484
     
    The association between ATM variants and risk of breast cancer: a systematic review and meta-analysis
    Moslemi M, Moradi Y, Dehghanbanadaki H, Afkhami H, Khaledi M, Sedighimehr N, Fathi J, Sohrabi E
    BMC Cancer 2021 Jan 5;21(1):27.
    PMID 33402103
     
    Vulnerability to low-dose combination of irinotecan and niraparib in ATM-mutated colorectal cancer
    Vitiello PP, Martini G, Mele L, Giunta EF, De Falco V, Ciardiello D, Belli V, Cardone C, Matrone N, Poliero L, Tirino V, Napolitano S, Della Corte C, Selvaggi F, Papaccio G, Troiani T, Morgillo F, Desiderio V, Ciardiello F, Martinelli E
    J Exp Clin Cancer Res 2021 Jan 6;40(1):15.
    PMID 33407715
     
    Clinical Significance of Germline Cancer Predisposing Variants in Unselected Patients with Pancreatic Adenocarcinoma
    Fountzilas E, Eliades A, Koliou GA, Achilleos A, Loizides C, Tsangaras K, Pectasides D, Sgouros J, Papakostas P, Rallis G, Psyrri A, Papadimitriou C, Oikonomopoulos G, Ferentinos K, Koumarianou A, Zarkavelis G, Dervenis C, Aravantinos G, Bafaloukos D, Kosmidis P, Papaxoinis G, Theochari M, Varthalitis I, Kentepozidis N, Rigakos G, Saridaki Z, Nikolaidi A, Christopoulou A, Fostira F, Samantas E, Kypri E, Ioannides M, Koumbaris G, Fountzilas G, Patsalis PC
    Cancers (Basel) 2021 Jan 8;13(2):198.
    PMID 33429865
     
    The mutational repertoire of uterine sarcomas and carcinosarcomas in a Brazilian cohort: A preliminary study
    da Costa LT, Dos Anjos LG, Kagohara LT, Torrezan GT, De Paula CAA, Baracat EC, Carraro DM, Carvalho KC
    Clinics (Sao Paulo) 2021 Jan 20;76:e2324.
    PMID 33503190
     
    Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated ( ATM) Gene are Associated with High and Moderate Risks for Multiple Cancers
    Hall MJ, Bernhisel R, Hughes E, Larson K, Rosenthal ET, Singh NA, Lancaster JM, Kurian AW
    Cancer Prev Res (Phila) 2021 Apr;14(4):433-440.
    PMID 33509806
     
    Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
    Zengin T, Önal-Süzek T
    J Pers Med 2021 Feb 23;11(2):154.
    PMID 33672117
     
    Clonal evolution of T-cell chronic lymphocytic leukaemia in a patient with ataxia telangiectasia
    Taylor AM, Butterworth SV
    Int J Cancer 1986 Apr 15;37(4):511-6.
    PMID 3485581
     
    The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitts and an inv(14) T cell lymphoma
    Kennaugh AA, Butterworth SV, Hollis R, Baer R, Rabbitts TH, Taylor AM
    Hum Genet 1986 Jul;73(3):254-9.
    PMID 3488254
     
    A subpopulation of t(2;14)(p11;q32) cells in ataxia telangiectasia B lymphocytes
    Butterworth SV, Taylor AM
    Hum Genet 1986 Aug;73(4):346-9.
    PMID 3488948
     
    Cerebellar pathology in ataxia-telangiectasia: the significance of basket cells
    Gatti RA, Vinters HV
    Kroc Found Ser 1985;19:225-32.
    PMID 3864937
     
    Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia-telangiectasia
    Vinters HV, Gatti RA, Rakic P
    Kroc Found Ser 1985;19:233-55.
    PMID 3864938
     
    Diabetes mellitus in ataxia-telangiectasia, Fanconi anemia, xeroderma pigmentosum, common variable immune deficiency, and severe combined immune deficiency families
    Morrell D, Chase CL, Kupper LL, Swift M
    Diabetes 1986 Feb;35(2):143-7.
    PMID 3943665
     
    Cells from patients with ataxia telangiectasia are abnormally sensitive to the cytotoxic effect of a tumor promoter, phorbol-12-myristate-13-acetate
    Shiloh Y, Tabor E, Becker Y
    Mutat Res 1985 Apr;149(2):283-6.
    PMID 3982447
     
    An unusual form of diabetes mellitus in ataxia telangiectasia
    Schalch DS, McFarlin DE, Barlow MH
    N Engl J Med 1970 Jun 18;282(25):1396-402.
    PMID 4192270
     
    Radiation reaction in ataxia telangiectasia
    Morgan JL, Holcomb TM, Morrissey RW
    Am J Dis Child 1968 Nov;116(5):557-8.
    PMID 5687489
     
    Cutaneous manifestations of ataxia-telangiectasia
    Reed WB, Epstein WL, Boder E, Sedgwick R
    JAMA 1966 Feb 28;195(9):746-53.
    PMID 5951880
     
    Ataxia telangiectasia. Neoplasia, untoward response to x-irradiation, and tuberous sclerosis
    Gotoff SP, Amirmokri E, Liebner EJ
    Am J Dis Child 1967 Dec;114(6):617-25.
    PMID 6072741
     
    Cancer and cardiac deaths in obligatory ataxia-telangiectasia heterozygotes
    Swift M, Chase C
    Lancet 1983 May 7;1(8332):1049-50.
    PMID 6133091
     
    Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents
    Jaspers NG, de Wit J, Regulski MR, Bootsma D
    Cancer Res 1982 Jan;42(1):335-41.
    PMID 6172195
     
    Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts
    Shiloh Y, Tabor E, Becker Y
    Cancer Res 1982 Jun;42(6):2247-9.
    PMID 6210429
     
    Ataxia-Telangiectasia: a multiparameter analysis of eight families
    Gatti RA, Bick M, Tam CF, Medici MA, Oxelius VA, Holland M, Goldstein AL, Boder E
    Clin Immunol Immunopathol 1982 May;23(2):501-16.
    PMID 6213343
     
    Colony-forming ability of ataxia-telangiectasia skin fibroblasts is an indicator of their early senescence and increased demand for growth factors
    Shiloh Y, Tabor E, Becker Y
    Exp Cell Res 1982 Jul;140(1):191-9.
    PMID 6213420
     
    Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNA via a targeted free radical mechanism
    Shiloh Y, Tabor E, Becker Y
    Carcinogenesis 1983 Oct;4(10):1317-22.
    PMID 6616760
     
    Unrepaired DNA strand breaks in irradiated ataxia telangiectasia lymphocytes suggested from cytogenetic observations
    Taylor AM
    Mutat Res 1978 Jun;50(3):407-18.
    PMID 672922
     
    Defective DNA repair and increased lethality in ataxia telangiectasia cells exposed to 4-nitroquinoline-1-oxide
    Smith PJ, Paterson MC
    Nature 1980 Oct 23;287(5784):747-9.
    PMID 6776412
     
    Hypersensitivity of ataxia telangiectasia skin fibroblasts to DNA alkylating agents
    Barfknecht TR, Little JB
    Mutat Res 1982 Jun;94(2):369-82.
    PMID 6810166
     
    The response of a variety of human fibroblast cell strains to the lethal effects of alkylating agents
    Teo IA, Arlett CF
    Carcinogenesis 1982;3(1):33-7.
    PMID 7067035
     
    Malignancy, DNA damage and chromosomal aberrations in ataxia telangiectasia
    Taylor AM, Edwards MJ
    IARC Sci Publ 1982;(39):119-26.
    PMID 7152604
     
    Decreased DNA repair synthesis and defective colony-forming ability of ataxia telangiectasia fibroblast cell strains treated with N-methyl-N'-nitro-N-nitrosoguanidine
    Scudiero DA
    Cancer Res 1980 Apr;40(4):984-90.
    PMID 7357564
     
    DNA repair in lymphoblastoid cell lines established from human genetic disorders
    Henderson EE, Ribecky R
    Chem Biol Interact 1980 Dec;33(1):63-81.
    PMID 7438293
     
    Chromosome end associations, telomeres and telomerase activity in ataxia telangiectasia cells
    Pandita TK, Pathak S, Geard CR
    Cytogenet Cell Genet 1995;71(1):86-93.
    PMID 7606935
     
    ATM-related genes: what do they tell us about functions of the human gene?
    Zakian VA
    Cell 1995 Sep 8;82(5):685-7.
    PMID 7671296
     
    The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene
    Hari KL, Santerre A, Sekelsky JJ, McKim KS, Boyd JB, Hawley RS
    Cell 1995 Sep 8;82(5):815-21.
    PMID 7671309
     
    TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene
    Greenwell PW, Kronmal SL, Porter SE, Gassenhuber J, Obermaier B, Petes TD
    Cell 1995 Sep 8;82(5):823-9.
    PMID 7671310
     
    Ataxia-telangiectasia
    Gatti RA
    Dermatol Clin 1995 Jan;13(1):1-6.
    PMID 7712635
     
    A single ataxia telangiectasia gene with a product similar to PI-3 kinase
    Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y
    Science 1995 Jun 23;268(5218):1749-53.
    PMID 7792600
     
    Cancer risks in A-T heterozygotes
    Easton DF
    Int J Radiat Biol 1994 Dec;66(6 Suppl):S177-82.
    PMID 7836845
     
    Response of fibroblast cultures from ataxia-telangiectasia patients to reactive oxygen species generated during inflammatory reactions
    Ward AJ, Olive PL, Burr AH, Rosin MP
    Environ Mol Mutagen 1994;24(2):103-11.
    PMID 7925323
     
    Unusual sensitivity of ataxia telangiectasia cells to bleomycin
    Taylor AM, Rosney CM, Campbell JB
    Cancer Res 1979 Mar;39(3):1046-50.
    PMID 85479
     
    The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species
    Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G
    Hum Mol Genet 1995 Nov;4(11):2025-32.
    PMID 8589678
     
    Insulin-resistant diabetes mellitus in a black woman with ataxia-telangiectasia
    Blevins LS, Gebhart SS
    South Med J 1996 Jun;89(6):619-21.
    PMID 8638204
     
    Genomic Organization of the ATM gene
    Uziel T, Savitsky K, Platzer M, Ziv Y, Helbitz T, Nehls M, Boehm T, Rosenthal A, Shiloh Y, Rotman G
    Genomics 1996 Apr 15;33(2):317-20.
    PMID 8660985
     
    Accelerated telomere shortening in ataxia telangiectasia
    Metcalfe JA, Parkhill J, Campbell L, Stacey M, Biggs P, Byrd PJ, Taylor AM
    Nat Genet 1996 Jul;13(3):350-3.
    PMID 8673136
     
    Atm-deficient mice: a paradigm of ataxia telangiectasia
    Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A
    Cell 1996 Jul 12;86(1):159-71.
    PMID 8689683
     
    Induction of p53 and increased sensitivity to cisplatin in ataxia-telangiectasia cells
    Zhang N, Song Q, Lu H, Lavin MF
    Oncogene 1996 Aug 1;13(3):655-9.
    PMID 8760308
     
    Reduced telomere length in ataxia-telangiectasia fibroblasts
    Xia SJ, Shammas MA, Shmookler Reis RJ
    Mutat Res 1996 Sep 2;364(1):1-11.
    PMID 8814333
     
    Predominance of null mutations in ataxia-telangiectasia
    Gilad S, Khosravi R, Shkedy D, Uziel T, Ziv Y, Savitsky K, Rotman G, Smith S, Chessa L, Jorgensen TJ, Harnik R, Frydman M, Sanal O, Portnoi S, Goldwicz Z, Jaspers NG, Gatti RA, Lenoir G, Lavin MF, Tatsumi K, Wegner RD, Shiloh Y, Bar-Shira A
    Hum Mol Genet 1996 Apr;5(4):433-9.
    PMID 8845835
     
    The ataxia-telangiectasia gene product, a constitutively expressed nuclear protein that is not up-regulated following genome damage
    Brown KD, Ziv Y, Sadanandan SN, Chessa L, Collins FS, Shiloh Y, Tagle DA
    Proc Natl Acad Sci U S A 1997 Mar 4;94(5):1840-5.
    PMID 9050866
     
    Heterozygous ATM mutations do not contribute to early onset of breast cancer
    FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ, Haber DA
    Nat Genet 1997 Mar;15(3):307-10.
    PMID 9054948
     
    CAND3: a ubiquitously expressed gene immediately adjacent and in opposite transcriptional orientation to the ATM gene at 11q23.1
    Chen X, Yang L, Udar N, Liang T, Uhrhammer N, Xu S, Bay JO, Wang Z, Dandakar S, Chiplunkar S, Klisak I, Telatar M, Yang H, Concannon P, Gatti RA
    Mamm Genome 1997 Feb;8(2):129-33.
    PMID 9060412
     
    Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic DNA containing the entire ATM gene
    Platzer M, Rotman G, Bauer D, Uziel T, Savitsky K, Bar-Shira A, Gilad S, Shiloh Y, Rosenthal A
    Genome Res 1997 Jun;7(6):592-605.
    PMID 9199932
     
    Recombinant ATM protein complements the cellular A-T phenotype
    Ziv Y, Bar-Shira A, Pecker I, Russell P, Jorgensen TJ, Tsarfati I, Shiloh Y
    Oncogene 1997 Jul 10;15(2):159-67.
    PMID 9244351
     
    Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia
    Vorechovský I, Luo L, Dyer MJ, Catovsky D, Amlot PL, Yaxley JC, Foroni L, Hammarström L, Webster AD, Yuille MA
    Nat Genet 1997 Sep;17(1):96-9.
    PMID 9288106
     
    Biallelic mutations in the ATM gene in T-prolymphocytic leukemia
    Stilgenbauer S, Schaffner C, Litterst A, Liebisch P, Gilad S, Bar-Shira A, James MR, Lichter P, Döhner H
    Nat Med 1997 Oct;3(10):1155-9.
    PMID 9334731
     
    The ATM gene and protein: possible roles in genome surveillance, checkpoint controls and cellular defence against oxidative stress
    Rotman G, Shiloh Y
    Cancer Surv 1997;29:285-304.
    PMID 9338105
     
    Ataxia-telangiectasia: is ATM a sensor of oxidative damage and stress?
    Rotman G, Shiloh Y
    Bioessays 1997 Oct;19(10):911-7.
    PMID 9363685
     
    Cell-cycle signaling: Atm displays its many talents
    Westphal CH
    Curr Biol 1997 Dec 1;7(12):R789-92.
    PMID 9382823
     
    Influence of ATM function on telomere metabolism
    Smilenov LB, Morgan SE, Mellado W, Sawant SG, Kastan MB, Pandita TK
    Oncogene 1997 Nov 27;15(22):2659-65.
    PMID 9400992
     
    Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart
    Shiloh Y
    Annu Rev Genet 1997;31:635-62.
    PMID 9442910
     
    Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations
    Telatar M, Teraoka S, Wang Z, Chun HH, Liang T, Castellvi-Bel S, Udar N, Borresen-Dale AL, Chessa L, Bernatowska-Matuszkiewicz E, Porras O, Watanabe M, Junker A, Concannon P, Gatti RA
    Am J Hum Genet 1998 Jan;62(1):86-97.
    PMID 9443866
     
    Critical telomere shortening regulated by the ataxia-telangiectasia gene acts as a DNA damage signal leading to activation of p53 protein and limited life-span of human diploid fibroblasts. A review
    Vaziri H
    Biochemistry (Mosc) 1997 Nov;62(11):1306-10.
    PMID 9467855
     
    Requirements for p53 and the ATM gene product in the regulation of G1/S and S phase checkpoints
    Xie G, Habbersett RC, Jia Y, Peterson SR, Lehnert BE, Bradbury EM, D', Anna JA
    Oncogene 1998 Feb 12;16(6):721-36.
    PMID 9488036
     
    ATM is usually rearranged in T-cell prolymphocytic leukaemia
    Yuille MA, Coignet LJ, Abraham SM, Yaqub F, Luo L, Matutes E, Brito-Babapulle V, Vorechovský I, Dyer MJ, Catovsky D
    Oncogene 1998 Feb 12;16(6):789-96.
    PMID 9488043
     
    Genotype-phenotype relationships in ataxia-telangiectasia and variants
    Gilad S, Chessa L, Khosravi R, Russell P, Galanty Y, Piane M, Gatti RA, Jorgensen TJ, Shiloh Y, Bar-Shira A
    Am J Hum Genet 1998 Mar;62(3):551-61.
    PMID 9497252
     
    Deficiency of the ATM protein expression defines an aggressive subgroup of B-cell chronic lymphocytic leukemia
    Starostik P, Manshouri T, O', Brien S, Freireich E, Kantarjian H, Haidar M, Lerner S, Keating M, Albitar M
    Cancer Res 1998 Oct 15;58(20):4552-7.
    PMID 9788599
     
    Ataxia telangiectasia
    Crawford TO
    Semin Pediatr Neurol 1998 Dec;5(4):287-94.
    PMID 9874856
     
    ATM mutations in B-cell chronic lymphocytic leukemia
    Bullrich F, Rasio D, Kitada S, Starostik P, Kipps T, Keating M, Albitar M, Reed JC, Croce CM
    Cancer Res 1999 Jan 1;59(1):24-7.
    PMID 9892178
     
    Classification of Tumours of Haematopoietic and Lymphoid Tissues.
    Swerdlow SH, Webber SA, Chadburn A, et al.
    Lyon : IARC press; 2008: 343-349. ISBN:978-92-832-2431-0
     

    Citation

    This paper should be referenced as such :
    Huret JL
    ATM (ataxia telangiectasia mutated);
    Atlas Genet Cytogenet Oncol Haematol. in press
    History of this paper:
    Huret, JL. ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. 1998;2(3):77-78.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37430/04-1998-ATM123.pdf
    Uhrhammer, N ; Bay, JO ; Gatti, RA. ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):173-174.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37550/10-1999-ATM123.pdf
    Uhrhammer, N ; Bay, JO ; Gatti, RA. ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):12-13.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37923/11-2002-ATM123.pdf
    Yossi Shiloh. ATM (ataxia telangiectasia mutated). Atlas Genet Cytogenet Oncol Haematol. 2017;21(7):237-248.
    http://documents.irevues.inist.fr/bitstream/handle/2042/68260/10-2016-ATMID123.pdf


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 27 ]
      Classification of B-cell chronic lymphoproliferative disorders (CLD)
    Burkitt's lymphoma (BL)
    Chronic lymphocytic leukaemia (CLL)
    Chronic myelogenous leukaemia (CML)
    del(11q) in non-Hodgkin's lymphoma (NHL)
    Del(6q) in Chronic lymphocytic leukaemia (CLL)
    dic(9;17)(p13;q11) PAX5::TAOK1
    Mantle cell lymphoma
    Small lymphocytic lymphoma
    t(1;3)(q25;q27) GAS5::BCL6
    t(3;3)(q27;q27) ST6GAL1::BCL6::del(3)(q27q27) ST6GAL1::BCL6
    t(3;6)(q27;p22) HIST1H4I::BCL6
    t(3;6)(q27;q14) SNHG5::BCL6
    t(3;6)(q27;q15) ?::BCL6
    t(3;7)(q27;q32) FRA7H::BCL6
    t(3;9)(q27;p13) GRHPR::BCL6
    t(3;9)(q27;p24) DMRT1::BCL6
    t(3;11)(q27;q23) POU2AF1::BCL6
    t(3;12)(q27;p12) LRMP::BCL6
    t(3;14)(q27;q32) HSP90AA1::BCL6
    t(3;19)(q27;q13) NAPA::BCL6
    t(6;9)(p22;q34) DEK::NUP214
    t(6;9)(p22;q34) DEK::NUP214 in Childhood
    Classification of T-Cell disorders
    T-cell::histiocyte rich large B-cell lymphoma
    T-cell prolymphocytic leukemia (T-PLL)
    t(X;14)(q28;q11.2) TRA-TRD::MTCP1::t(X;7)(q28;q34) TRB::MTCP1


    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
      Ataxia telangiectasia (A-T) Hereditary breast cancer


    External links

     

    Nomenclature
    HGNC (Hugo)ATM   795
    LRG (Locus Reference Genomic)LRG_135
    Cards
    AtlasATMID123
    Entrez_Gene (NCBI)ATM    ATM serine/threonine kinase
    AliasesAT1; ATA; ATC; ATD; 
    ATDC; ATE; TEL1; TELO1
    GeneCards (Weizmann)ATM
    Ensembl hg19 (Hinxton)ENSG00000149311 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000149311 [Gene_View]  ENSG00000149311 [Sequence]  chr11:108223529-108229364 [Contig_View]  ATM [Vega]
    ICGC DataPortalENSG00000149311
    TCGA cBioPortalATM
    AceView (NCBI)ATM
    Genatlas (Paris)ATM
    SOURCE (Princeton)ATM
    Genetics Home Reference (NIH)ATM
    Genomic and cartography
    GoldenPath hg38 (UCSC)ATM  -     chr11:108223529-108229364 +  11q22.3   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)ATM  -     11q22.3   [Description]    (hg19-Feb_2009)
    GoldenPathATM - 11q22.3 [CytoView hg19]  ATM - 11q22.3 [CytoView hg38]
    ImmunoBaseENSG00000149311
    Genome Data Viewer NCBIATM [Mapview hg19]  
    OMIM114480   208900   607585   
    Gene and transcription
    Genbank (Entrez)AB209133 AF035326 AF035327 AF035328 AI479273
    RefSeq transcript (Entrez)NM_000051 NM_001351834 NM_001351835 NM_001351836 NM_138292 NM_138293
    Consensus coding sequences : CCDS (NCBI)ATM
    Gene ExpressionATM [ NCBI-GEO ]   ATM [ EBI - ARRAY_EXPRESS ]   ATM [ SEEK ]   ATM [ MEM ]
    Gene Expression Viewer (FireBrowse)ATM [ Firebrowse - Broad ]
    GenevisibleExpression of ATM in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)472
    GTEX Portal (Tissue expression)ATM
    Human Protein AtlasENSG00000149311-ATM [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ13315   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ13315  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ13315
    PhosPhoSitePlusQ13315
    Domaine pattern : Prosite (Expaxy)FAT (PS51189)    FATC (PS51190)    PI3_4_KINASE_1 (PS00915)    PI3_4_KINASE_2 (PS00916)    PI3_4_KINASE_3 (PS50290)   
    Domains : Interpro (EBI)ARM-type_fold    ATM/Tel1    FATC_dom    Kinase-like_dom_sf    PI3/4_kinase_cat_dom    PI3/4_kinase_cat_sf    PI3/4_kinase_CS    PIK-rel_kinase_FAT    PIK_FAT    PIKKc_ATM    TAN   
    Domain families : Pfam (Sanger)FAT (PF02259)    FATC (PF02260)    PI3_PI4_kinase (PF00454)    TAN (PF11640)   
    Domain families : Pfam (NCBI)pfam02259    pfam02260    pfam00454    pfam11640   
    Domain families : Smart (EMBL)FATC (SM01343)  PI3Kc (SM00146)  TAN (SM01342)  
    Conserved Domain (NCBI)ATM
    PDB (RSDB)5NP0    5NP1    6HKA    6K9K    6K9L   
    PDB Europe5NP0    5NP1    6HKA    6K9K    6K9L   
    PDB (PDBSum)5NP0    5NP1    6HKA    6K9K    6K9L   
    PDB (IMB)5NP0    5NP1    6HKA    6K9K    6K9L   
    Structural Biology KnowledgeBase5NP0    5NP1    6HKA    6K9K    6K9L   
    SCOP (Structural Classification of Proteins)5NP0    5NP1    6HKA    6K9K    6K9L   
    CATH (Classification of proteins structures)5NP0    5NP1    6HKA    6K9K    6K9L   
    SuperfamilyQ13315
    AlphaFold pdb e-kbQ13315   
    Human Protein Atlas [tissue]ENSG00000149311-ATM [tissue]
    HPRD06347
    Protein Interaction databases
    DIP (DOE-UCLA)Q13315
    IntAct (EBI)Q13315
    BioGRIDATM
    STRING (EMBL)ATM
    ZODIACATM
    Ontologies - Pathways
    QuickGOQ13315
    Ontology : AmiGODNA damage checkpoint signaling  pexophagy  telomere maintenance  DNA double-strand break processing  chromosome, telomeric region  chromosome, telomeric region  pre-B cell allelic exclusion  DNA binding  protein serine/threonine kinase activity  protein serine/threonine kinase activity  DNA-dependent protein kinase activity  protein binding  ATP binding  nucleus  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  peroxisomal matrix  centrosome  cytosol  DNA replication  double-strand break repair  double-strand break repair via nonhomologous end joining  protein phosphorylation  protein phosphorylation  cellular response to DNA damage stimulus  cellular response to DNA damage stimulus  cellular response to DNA damage stimulus  DNA damage induced protein phosphorylation  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  mitotic spindle assembly checkpoint signaling  mitotic G2 DNA damage checkpoint signaling  reciprocal meiotic recombination  signal transduction  intrinsic apoptotic signaling pathway in response to DNA damage  response to ionizing radiation  regulation of autophagy  positive regulation of gene expression  1-phosphatidylinositol-3-kinase activity  histone phosphorylation  peptidyl-serine phosphorylation  positive regulation of cell migration  negative regulation of B cell proliferation  cytoplasmic vesicle  regulation of telomere maintenance via telomerase  positive regulation of telomere maintenance via telomerase  phosphatidylinositol-3-phosphate biosynthetic process  peptidyl-serine autophosphorylation  identical protein binding  regulation of apoptotic process  positive regulation of apoptotic process  intracellular membrane-bounded organelle  positive regulation of DNA damage response, signal transduction by p53 class mediator  protein-containing complex binding  positive regulation of cell adhesion  positive regulation of transcription by RNA polymerase II  protein autophosphorylation  protein autophosphorylation  protein N-terminus binding  regulation of cell cycle  regulation of telomerase activity  histone mRNA catabolic process  cellular response to retinoic acid  cellular response to gamma radiation  cellular response to X-ray  cellular response to nitrosative stress  replicative senescence  establishment of RNA localization to telomere  establishment of protein-containing complex localization to telomere  protein serine kinase activity  protein threonine kinase activity  regulation of cellular response to heat  regulation of signal transduction by p53 class mediator  negative regulation of TORC1 signaling  negative regulation of TORC1 signaling  negative regulation of telomere capping  positive regulation of telomere maintenance via telomere lengthening  positive regulation of telomerase catalytic core complex assembly  DNA repair complex  
    Ontology : EGO-EBIDNA damage checkpoint signaling  pexophagy  telomere maintenance  DNA double-strand break processing  chromosome, telomeric region  chromosome, telomeric region  pre-B cell allelic exclusion  DNA binding  protein serine/threonine kinase activity  protein serine/threonine kinase activity  DNA-dependent protein kinase activity  protein binding  ATP binding  nucleus  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  peroxisomal matrix  centrosome  cytosol  DNA replication  double-strand break repair  double-strand break repair via nonhomologous end joining  protein phosphorylation  protein phosphorylation  cellular response to DNA damage stimulus  cellular response to DNA damage stimulus  cellular response to DNA damage stimulus  DNA damage induced protein phosphorylation  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  mitotic spindle assembly checkpoint signaling  mitotic G2 DNA damage checkpoint signaling  reciprocal meiotic recombination  signal transduction  intrinsic apoptotic signaling pathway in response to DNA damage  response to ionizing radiation  regulation of autophagy  positive regulation of gene expression  1-phosphatidylinositol-3-kinase activity  histone phosphorylation  peptidyl-serine phosphorylation  positive regulation of cell migration  negative regulation of B cell proliferation  cytoplasmic vesicle  regulation of telomere maintenance via telomerase  positive regulation of telomere maintenance via telomerase  phosphatidylinositol-3-phosphate biosynthetic process  peptidyl-serine autophosphorylation  identical protein binding  regulation of apoptotic process  positive regulation of apoptotic process  intracellular membrane-bounded organelle  positive regulation of DNA damage response, signal transduction by p53 class mediator  protein-containing complex binding  positive regulation of cell adhesion  positive regulation of transcription by RNA polymerase II  protein autophosphorylation  protein autophosphorylation  protein N-terminus binding  regulation of cell cycle  regulation of telomerase activity  histone mRNA catabolic process  cellular response to retinoic acid  cellular response to gamma radiation  cellular response to X-ray  cellular response to nitrosative stress  replicative senescence  establishment of RNA localization to telomere  establishment of protein-containing complex localization to telomere  protein serine kinase activity  protein threonine kinase activity  regulation of cellular response to heat  regulation of signal transduction by p53 class mediator  negative regulation of TORC1 signaling  negative regulation of TORC1 signaling  negative regulation of telomere capping  positive regulation of telomere maintenance via telomere lengthening  positive regulation of telomerase catalytic core complex assembly  DNA repair complex  
    Pathways : BIOCARTAcdc25 and chk1 Regulatory Pathway in response to DNA damage [Genes]    RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage [Genes]    Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility [Genes]    p53 Signaling Pathway [Genes]    ATM Signaling Pathway [Genes]    Apoptotic Signaling in Response to DNA Damage [Genes]    Cell Cycle: G1/S Check Point [Genes]    Hypoxia and p53 in the Cardiovascular system [Genes]    Cell Cycle: G2/M Checkpoint [Genes]    Regulation of cell cycle progression by Plk3 [Genes]   
    Pathways : KEGGNF-kappa B signaling pathway    FoxO signaling pathway    Cell cycle    p53 signaling pathway    Apoptosis    HTLV-I infection    Transcriptional misregulation in cancer    MicroRNAs in cancer   
    REACTOMEQ13315 [protein]
    REACTOME PathwaysR-HSA-912446 [pathway]   
    NDEx NetworkATM
    Atlas of Cancer Signalling NetworkATM
    Wikipedia pathwaysATM
    Orthology - Evolution
    OrthoDB472
    GeneTree (enSembl)ENSG00000149311
    Phylogenetic Trees/Animal Genes : TreeFamATM
    Homologs : HomoloGeneATM
    Homology/Alignments : Family Browser (UCSC)ATM
    Gene fusions - Rearrangements
    Fusion : MitelmanJARID2::ATM [6p22.3/11q22.3]  
    Fusion : QuiverATM
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerATM [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)ATM
    dbVarATM
    ClinVarATM
    MonarchATM
    1000_GenomesATM 
    Exome Variant ServerATM
    GNOMAD BrowserENSG00000149311
    Varsome BrowserATM
    ACMGATM variants
    VarityQ13315
    Genomic Variants (DGV)ATM [DGVbeta]
    DECIPHERATM [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisATM 
    Mutations
    ICGC Data PortalATM 
    TCGA Data PortalATM 
    Broad Tumor PortalATM
    OASIS PortalATM [ Somatic mutations - Copy number]
    Cancer Gene: CensusATM 
    Somatic Mutations in Cancer : COSMICATM  [overview]  [genome browser]  [tissue]  [distribution]  
    Somatic Mutations in Cancer : COSMIC3DATM
    Mutations and Diseases : HGMDATM
    intOGen PortalATM
    LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
    BioMutaATM
    DgiDB (Drug Gene Interaction Database)ATM
    DoCM (Curated mutations)ATM
    CIViC (Clinical Interpretations of Variants in Cancer)ATM
    OncoKBATM
    NCG (London)ATM
    Cancer3DATM
    Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM114480    208900    607585   
    Orphanet104    22485    22484    10899    10693   
    DisGeNETATM
    MedgenATM
    Genetic Testing Registry ATM
    NextProtQ13315 [Medical]
    GENETestsATM
    Target ValidationATM
    Huge Navigator ATM [HugePedia]
    ClinGenATM
    Clinical trials, drugs, therapy
    MyCancerGenomeATM
    Protein Interactions : CTDATM
    Pharm GKB GenePA61
    Pharm GKB PathwaysPA165948566   PA166115250   
    PharosQ13315
    Clinical trialATM
    Miscellaneous
    canSAR (ICR)ATM
    HarmonizomeATM
    DataMed IndexATM
    Probes
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    EVEXATM
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Oct 8 21:12:54 CEST 2021

    Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.