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

ALK (anaplastic lymphoma receptor tyrosine kinase)

Written1997-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2001-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France
Updated2003-08Jean-Loup Huret, Sylvie Senon
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2010-02Michèle Allouche
INSERM U.563 CPTP, Bat. B, Pavillon Lefevre, CHU Purpan, BP 3028, 31024 Toulouse Cedex 3, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesanaplastic lymphoma kinase (Ki-1)
Alias_symbol (synonym)CD246
Other alias
HGNC (Hugo) ALK
LocusID (NCBI) 238
Atlas_Id 16
Location 2p23.2  [Link to chromosome band 2p23]
Location_base_pair Starts at 29192774 and ends at 29921611 bp from pter ( according to hg19-Feb_2009)  [Mapping ALK.png]
 
  ALK (2p23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2016)		A2M (12p13.31) / ALK (2p23.2)ALK (2p23.2) / ALO17 ()ALK (2p23.2) / ATIC (2q35)
ALK (2p23.2) / CARS (11p15.4)ALK (2p23.2) / CLTC (17q23.1)ALK (2p23.2) / EML4 (2p21)
ALK (2p23.2) / KIF5B (10p11.22)ALK (2p23.2) / MSN (Xq12)ALK (2p23.2) / MYH9 (22q12.3)
ALK (2p23.2) / NPM1 (5q35.1)ALK (2p23.2) / PQLC3 (2p25.1)ALK (2p23.2) / PTPN3 (9q31.3)
ALK (2p23.2) / RANBP2 (2q12.3)ALK (2p23.2) / RNPC3 (1p21.1)ALK (2p23.2) / ROS1 (6q22.1)
ALK (2p23.2) / RPA1 (17p13.3)ALK (2p23.2) / TFG (3q12.2)ALK (2p23.2) / TPM3 (1q21.3)
ALK (2p23.2) / TPM4 (19p13.12)ATIC (2q35) / ALK (2p23.2)C2orf44 (2p23.3) / ALK (2p23.2)
C2orf61 (2p21) / ALK (2p23.2)CARS (11p15.4) / ALK (2p23.2)CLTA (9p13.3) / ALK (2p23.2)
CLTC (17q23.1) / ALK (2p23.2)CLTCL1 (22q11.21) / ALK (2p23.2)DCTN1 (2p13.1) / ALK (2p23.2)
EML4 (2p21) / ALK (2p23.2)FN1 (2q35) / ALK (2p23.2)GALM (2p22.1) / ALK (2p23.2)
GTF2IRD1 (7q11.23) / ALK (2p23.2)HIP1 (7q11.23) / ALK (2p23.2)KCNQ5 (6q13) / ALK (2p23.2)
KIF5B (10p11.22) / ALK (2p23.2)KLC1 (14q32.33) / ALK (2p23.2)LMNA (1q22) / ALK (2p23.2)
MALAT1 (11q13.1) / ALK (2p23.2)MSN (Xq12) / ALK (2p23.2)MYH9 (22q12.3) / ALK (2p23.2)
NPM1 (5q35.1) / ALK (2p23.2)PPFIBP1 (12p11.23) / ALK (2p23.2)PPP4R3B (2p16.1) / ALK (2p23.2)
PRKAR1A (17q24.2) / ALK (2p23.2)RANBP2 (2q12.3) / ALK (2p23.2)RNF213 (17q25.3) / ALK (2p23.2)
SEC31A (4q21.22) / ALK (2p23.2)SQSTM1 (5q35.3) / ALK (2p23.2)STRN (2p22.2) / ALK (2p23.2)
TERT (5p15.33) / ALK (2p23.2)TFG (3q12.2) / ALK (2p23.2)TPM1 (15q22.2) / ALK (2p23.2)
TPM3 (1q21.3) / ALK (2p23.2)TPM4 (19p13.12) / ALK (2p23.2)TPR (1q31.1) / ALK (2p23.2)
TRAF1 (9q33.2) / ALK (2p23.2)TRMT61B (2p23.2) / ALK (2p23.2)VCL (10q22.2) / ALK (2p23.2)

DNA/RNA

Description The gene is composed of 29 exons spanning in a region of 728793 bp.
Transcription 6226 bp cDNA; coding sequence: 4.9 kb.

Protein

 
Description 1620 amino acids; 177 kDa; after glycosylation, produces a 200 kDa mature glycoprotein; type I transmembrane receptor; composed of an extracellular region (containing two MAM and one LDLa domains, and one glycin-rich region), a transmembrane, and an intracellular region (composed of a juxta-membrane domain, a tyrosine kinase domain (1122-1376), and a C-terminal domain; dimerization.
Expression Is tissue specific; mainly in: central and peripheral nervous system during development (less in adult), and testis; not in the lymphocytes.
Localisation Cell membrane.
Function ALK is a membrane associated tyrosine kinase receptor of the insulin receptor superfamily. The function of the full-length ALK receptor is poorly understood. It has a probable role in the central and peripheral nervous system development and maintenance. ALK is a dependence receptor, which may exert antagonist functions, proapoptotic or antiapoptotic, depending on the absence or presence of a ligand (Mourali et al., 2006). Dependence receptors have a potential role in cancer and development (Allouche, 2007). Ligands available for this demonstration were agonist anti-ALK antibodies (Motegi et al., 2004; Moog-Lutz et al., 2005). If a specific ALK ligand (jelly belly) has been clearly identified in Drosophila, it has no homologue in vertebrates (Palmer et al., 2009). ALK is still an orphan receptor, given the high level of controversy about pleiotrophin and midkine, which have been proposed as ligands by Stoica et al. (2001, 2002) (see review by Chiarle et al., 2008).
Homology Homologies with the insulin receptor super family: LTK (leucocyte tyrosine kinase), IGF1-R, IRb, TRKA, ROS (homolog of the drosophila Sevenless).

Implicated in

Note
  
Entity ALK+ anaplastic large cell lymphoma (ALCL)
Disease ALCL are high grade non Hodgkin lymphomas. ALK+ ALCL are ALCL where ALK is involved in a fusion gene; systemic ALK+ ALCL (as opposed to cutaneous ALCL, which are usually ALK negative) represent 60 to 80 % of ALCL cases (they are CD30+, ALK+); 70 to 80% of ALK+ ALCL cases bear a t(2;5); the remaining ALK+ ALCL cases bear variant translocations X-ALK, where X designates a partner gene.
Prognosis Although presenting as a high grade tumour, an 80% five year survival is associated with this anomaly, but recurrence is a concern.
Cytogenetics The prototype anomaly is the t(2;5)(p23;q35) generating the NPM1-ALK fusion.
Alternative anomalies involving the ALK gene in ALCL are described below as cytoplasmic ALK+ ALCL cases, among which the t(1;2) TPM3-ALK is found in 20% of ALK+ ALCL.
Complex karyotypes may also be found.
Hybrid/Mutated Gene 5' NPM1 - 3' ALK on the der(5).
Abnormal Protein 680 amino acids, 80 kDa; N-term 117 amino acids from NPM1 fused to the 563 C-term amino acids of ALK (i.e. composed of the oligomerization domain and the metal binding site of NPM1, and the entire cytoplasmic portion of ALK); no apparent expression of the ALK/NPM1 counterpart. Characteristic localisation in the cytoplasm, nucleus and nucleolus, due to heterooligomerization of NPM1-ALK and normal NPM1 whereas the normal NPM1 protein is confined to the nucleus and nucleolus; constitutive activation of the catalytic domain of ALK.
Oncogenesis Via the kinase function activated by oligomerization of NPM1-ALK mediated by the NPM1 part.
  
  
Entity Cytoplasmic ALK+ anaplasic large cell lymphoma (ALCL)
Prognosis Present a favourable prognosis comparable to the one found in t(2;5) ALK+ ALCL.
Cytogenetics Either t(X;2)(q11;p23), t(1;2)(q25;p23), inv(2)(p23q35), t(2;3)(p23;q21), t(2;17)(p23;q23), t(2;17)(p23;q25), t(2;19)(p23;p13.1) or t(2;22)(p23;q11.2).
Hybrid/Mutated Gene 5' MSN, TPM3, ATIC, TFG, CLTC, ALO17, TPM4 or MYH9 - 3' ALK.
Abnormal Protein N-term amino acids from the partner gene fused to the 563 C-term amino acids (in the great majority of cases) from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); cytoplasmic/membraneous localisation only.
Oncogenesis The partner gene seems to provoke the dimerization of the fused X-ALK, which should lead to constitutive autophosphorylation and activation of the ALK tyrosine kinase, as for NPM1-ALK (see t(2;5)(p23;q35)).
  
  
Entity Inflammatory myofibroblastic tumours with 2p23 rearrangements
Disease Rare soft tissue tumour found in children and young adults about one third to half of inflammatory myofibroblastic tumour cases present with a 2p23 rearrangement involving ALK.
Prognosis Good prognosis.
Cytogenetics t(1;2)(q25;p23), t(2;2)(p23;q13) or inv(2)(p23;q11-13), inv(2)(p23;q35), t(2;4)(p23;q21), t(2;11)(p23;p15), t(2;17)(p23;q23), or t(2;19)(p23;p13.1) so far.
Hybrid/Mutated Gene 5' TPM3 in the t(1;2), RANBP2 in the t(2;2) or inv(2)(p23;q11-13), 5' ATIC in inv(2)(p23;q35), 5' SEC31L1 in t(2;4), 5' CARS in the t(2;11), 5' CLTC in the t(2;17), or 5' TPM4 in the t(2;19) - 3' ALK.
Abnormal Protein N-term amino acids from the partner gene fused to the 563 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein is known or suspected.
Oncogenesis Fused-ALK is constitutively activated.
  
  
Entity ALK+ diffuse large B-cell lymphoma (DLBCL)
Disease Very rare form of DLBCL (40 cases described) expressing either ALK in fusion with CLTC (cytoplasmic granular localisation) associated to t(2;17)(p23;q23) (most frequently), or (rarely) NPM1-ALK in t(2;5)(p23;q35); tumours are EMA+, CD30- and CD20-negative.
Prognosis Poor prognosis: aggressive lymphoma with 25% five year survival.
Cytogenetics t(2;5)(p23;q35) or t(2;17)(p23;q23).
Hybrid/Mutated Gene 5' NPM1 or CLTC - 3' ALK.
Abnormal Protein N-term amino acids from the partner gene fused to the 563 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein is known or suspected.
Oncogenesis Fused-ALK is constitutively activated.
  
  
Entity ALK+ non-small cell lung cancer (NSCLC)
Disease 1-6 % of all NSCLC present a rearrangement involving ALK fused to EML4 in an inv(2)(p21p23); studies on East Asian and American/European patients (Soda et al., 2007; Perner et al., 2008).
Prognosis 50% survival at 24 months, so far (first identification in 2007).
Cytogenetics inv(2)(p21;p23).
Hybrid/Mutated Gene 5' EML4 - 3' ALK; multiple variants of EML4-ALK noted depending on the breakpoint on the EML gene; ALK fusion starts at a portion encoded by exon 20.
Abnormal Protein N-term amino acids from the partner gene fused to the 563 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein is known or suspected; protein is difficult to detect by classical immunohistochemistry methods (low expression).
Oncogenesis Fused-ALK is constitutively activated.
Note: in a European study, EML4-ALK fusion transcript has also been found in up to 9% non-tumour lung tissue from lung tumour patients. Interestingly, the EML4-ALK transcript was not detected in matching tumour samples from the same patients (Martelli et al., 2009).
  
  
Entity Familial neuroblastoma and sporadic neuroblastoma
Disease Neuroblastoma is a cancer of early childhood that arises from the developing autonomic nervous system, giving rise to peripheral tumours. It is the most common malignancy diagnosed in the first year of life and shows a wide range of clinical phenotypes, with a few patients having tumours that regress spontaneously, whereas most patients have aggressive metastatic disease. It can be transmitted in an autosomal dominant mode as a familial predisposition, or occur as a sporadic disease.
Prognosis Aggressive neuroblastoma cases have survival probabilities of less then 40% despite intensive chemoradiotherapy, and the disease continues to account for 15% of childhood cancer mortality.
Cytogenetics Gene amplifications or mutations of ALK;
Associated alterations: tumours from patients with an aggressive phenotype often show amplification of the MYCN oncogene, and/or deletions of chromosome arms 1p and 11q.
Hybrid/Mutated Gene Several point mutations located in the coding region of the receptor intracellular portion, mostly in the tyrosine kinase domain.
Abnormal Protein 54 ALK mutations reported, affecting 12 different residues (Caren et al., 2008; Chen et al., 2008; George et al., 2008; Janoueix-Lerosey et al., 2008; Mosse et al., 2008); two hotspots: F1174 and R1275.
Most frequent germline mutations (familial cases): G1128A, R1192P, R1275Q.
Most frequent somatic mutations (sporadic cases): F1174L/I, F1245C/V.
Oncogenesis Gene amplifications or point mutations both confer constitutive kinase activation.
  

Breakpoints

 
Note Most of the breakpoints occur in the same intron of ALK, whichever partner is involved in the fusion protein.

To be noted

ALK in fusion to several gene partners, is found implicated both in hematopoietic and non-hematopoietic solid tumours; this was a new concept in 2003, that several different types of tumour may result from the same chromosomal/genes rearrangement(s).

Bibliography

ALK is a novel dependence receptor: potential implications in development and cancer.
Allouche M.
Cell Cycle. 2007 Jul 1;6(13):1533-8. Epub 2007 May 14. (REVIEW)
PMID 17611412
 
Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.
Bischof D, Pulford K, Mason DY, Morris SW.
Mol Cell Biol. 1997 Apr;17(4):2312-25.
PMID 9121481
 
Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor.
Bridge JA, Kanamori M, Ma Z, Pickering D, Hill DA, Lydiatt W, Lui MY, Colleoni GW, Antonescu CR, Ladanyi M, Morris SW.
Am J Pathol. 2001 Aug;159(2):411-5.
PMID 11485898
 
Oncogenic mutations of ALK kinase in neuroblastoma.
Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa S.
Nature. 2008 Oct 16;455(7215):971-4.
PMID 18923524
 
The anaplastic lymphoma kinase in the pathogenesis of cancer.
Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G.
Nat Rev Cancer. 2008 Jan;8(1):11-23. (REVIEW)
PMID 18097461
 
ATIC-ALK: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35).
Colleoni GW, Bridge JA, Garicochea B, Liu J, Filippa DA, Ladanyi M.
Am J Pathol. 2000 Mar;156(3):781-9.
PMID 10702393
 
Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.
Cools J, Wlodarska I, Somers R, Mentens N, Pedeutour F, Maes B, De Wolf-Peeters C, Pauwels P, Hagemeijer A, Marynen P.
Genes Chromosomes Cancer. 2002 Aug;34(4):354-62.
PMID 12112524
 
Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor.
Debelenko LV, Arthur DC, Pack SD, Helman LJ, Schrump DS, Tsokos M.
Lab Invest. 2003 Sep;83(9):1255-65.
PMID 13679433
 
Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines.
Dirks WG, Fahnrich S, Lis Y, Becker E, MacLeod RA, Drexler HG.
Int J Cancer. 2002 Jul 1;100(1):49-56.
PMID 12115586
 
Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.
Drexler HG, Gignac SM, von Wasielewski R, Werner M, Dirks WG.
Leukemia. 2000 Sep;14(9):1533-59. (REVIEW)
PMID 10994999
 
Translocations involving anaplastic lymphoma kinase (ALK).
Duyster J, Bai RY, Morris SW.
Oncogene. 2001 Sep 10;20(40):5623-37. (REVIEW)
PMID 11607814
 
ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases.
Gascoyne RD, Lamant L, Martin-Subero JI, Lestou VS, Harris NL, Muller-Hermelink HK, Seymour JF, Campbell LJ, Horsman DE, Auvigne I, Espinos E, Siebert R, Delsol G.
Blood. 2003 Oct 1;102(7):2568-73. Epub 2003 May 22.
PMID 12763927
 
Activating mutations in ALK provide a therapeutic target in neuroblastoma.
George RE, Sanda T, Hanna M, Frohling S, Luther W 2nd, Zhang J, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregor VE, Webb TR, Gray NS, Gilliland DG, Diller L, Greulich H, Morris SW, Meyerson M, Look AT.
Nature. 2008 Oct 16;455(7215):975-8.
PMID 18923525
 
Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.
Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ.
Cancer Res. 1999 Jun 15;59(12):2776-80.
PMID 10383129
 
Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity.
Hernandez L, Bea S, Bellosillo B, Pinyol M, Falini B, Carbone A, Ott G, Rosenwald A, Fernandez A, Pulford K, Mason D, Morris SW, Santos E, Campo E.
Am J Pathol. 2002 Apr;160(4):1487-94.
PMID 11943732
 
Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system.
Iwahara T, Fujimoto J, Wen D, Cupples R, Bucay N, Arakawa T, Mori S, Ratzkin B, Yamamoto T.
Oncogene. 1997 Jan 30;14(4):439-49.
PMID 9053841
 
Molecular pathogenesis of peripheral neuroblastic tumors.
Janoueix-Lerosey I, Schleiermacher G, Delattre O.
Oncogene. 2010 Mar 18;29(11):1566-79. Epub 2010 Jan 25.
PMID 20101209
 
A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation.
Lamant L, Dastugue N, Pulford K, Delsol G, Mariame B.
Blood. 1999 May 1;93(9):3088-95.
PMID 10216106
 
Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma.
Lamant L, Gascoyne RD, Duplantier MM, Armstrong F, Raghab A, Chhanabhai M, Rajcan-Separovic E, Raghab J, Delsol G, Espinos E.
Genes Chromosomes Cancer. 2003 Aug;37(4):427-32.
PMID 12800156
 
High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining.
Lamant L, Meggetto F, al Saati T, Brugieres L, de Paillerets BB, Dastugue N, Bernheim A, Rubie H, Terrier-Lacombe MJ, Robert A, Rigal F, Schlaifer D, Shiuta M, Mori S, Delsol G.
Blood. 1996 Jan 1;87(1):284-91.
PMID 8547653
 
Expression of the ALK tyrosine kinase gene in neuroblastoma.
Lamant L, Pulford K, Bischof D, Morris SW, Mason DY, Delsol G, Mariame B.
Am J Pathol. 2000 May;156(5):1711-21.
PMID 10793082
 
TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.
Lawrence B, Perez-Atayde A, Hibbard MK, Rubin BP, Dal Cin P, Pinkus JL, Pinkus GS, Xiao S, Yi ES, Fletcher CD, Fletcher JA.
Am J Pathol. 2000 Aug;157(2):377-84.
PMID 10934142
 
Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive anaplastic lymphoma kinase (ALK) tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis.
Ma Z, Cools J, Marynen P, Cui X, Siebert R, Gesk S, Schlegelberger B, Peeters B, De Wolf-Peeters C, Wlodarska I, Morris SW.
Blood. 2000 Mar 15;95(6):2144-9.
PMID 10706887
 
Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer.
Mano H.
Cancer Sci. 2008 Dec;99(12):2349-55. Epub 2008 Nov 20. (REVIEW)
PMID 19032370
 
EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues.
Martelli MP, Sozzi G, Hernandez L, Pettirossi V, Navarro A, Conte D, Gasparini P, Perrone F, Modena P, Pastorino U, Carbone A, Fabbri A, Sidoni A, Nakamura S, Gambacorta M, Fernandez PL, Ramirez J, Chan JK, Grigioni WF, Campo E, Pileri SA, Falini B.
Am J Pathol. 2009 Feb;174(2):661-70. Epub 2009 Jan 15.
PMID 19147828
 
Activation and inhibition of anaplastic lymphoma kinase receptor tyrosine kinase by monoclonal antibodies and absence of agonist activity of pleiotrophin.
Moog-Lutz C, Degoutin J, Gouzi JY, Frobert Y, Brunet-de Carvalho N, Bureau J, Creminon C, Vigny M.
J Biol Chem. 2005 Jul 15;280(28):26039-48. Epub 2005 May 10.
PMID 15886198
 
Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT.
Science. 1994 Mar 4;263(5151):1281-4.
PMID 8122112
 
ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK).
Morris SW, Naeve C, Mathew P, James PL, Kirstein MN, Cui X, Witte DP.
Oncogene. 1997 May 8;14(18):2175-88.
PMID 9174053
 
Identification of ALK as a major familial neuroblastoma predisposition gene.
Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM.
Nature. 2008 Oct 16;455(7215):930-5. Epub 2008 Aug 24.
PMID 18724359
 
ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth.
Motegi A, Fujimoto J, Kotani M, Sakuraba H, Yamamoto T.
J Cell Sci. 2004 Jul 1;117(Pt 15):3319-29.
PMID 15226403
 
Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage.
Mourali J, Benard A, Lourenco FC, Monnet C, Greenland C, Moog-Lutz C, Racaud-Sultan C, Gonzalez-Dunia D, Vigny M, Mehlen P, Delsol G, Allouche M.
Mol Cell Biol. 2006 Aug;26(16):6209-22.
PMID 16880530
 
ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases.
Onciu M, Behm FG, Downing JR, Shurtleff SA, Raimondi SC, Ma Z, Morris SW, Kennedy W, Jones SC, Sandlund JT.
Blood. 2003 Oct 1;102(7):2642-4. Epub 2003 Jun 19.
PMID 12816858
 
Anaplastic lymphoma kinase: signalling in development and disease.
Palmer RH, Vernersson E, Grabbe C, Hallberg B.
Biochem J. 2009 May 27;420(3):345-61. (REVIEW)
PMID 19459784
 
Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor.
Panagopoulos I, Nilsson T, Domanski HA, Isaksson M, Lindblom P, Mertens F, Mandahl N.
Int J Cancer. 2006 Mar 1;118(5):1181-6.
PMID 16161041
 
EML4-ALK fusion lung cancer: a rare acquired event.
Perner S, Wagner PL, Demichelis F, Mehra R, Lafargue CJ, Moss BJ, Arbogast S, Soltermann A, Weder W, Giordano TJ, Beer DG, Rickman DS, Chinnaiyan AM, Moch H, Rubin MA.
Neoplasia. 2008 Mar;10(3):298-302.
PMID 18320074
 
The emerging normal and disease-related roles of anaplastic lymphoma kinase.
Pulford K, Lamant L, Espinos E, Jiang Q, Xue L, Turturro F, Delsol G, Morris SW.
Cell Mol Life Sci. 2004 Dec;61(23):2939-53. (REVIEW)
PMID 15583856
 
Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.
Shiota M, Nakamura S, Ichinohasama R, Abe M, Akagi T, Takeshita M, Mori N, Fujimoto J, Miyauchi J, Mikata A, Nanba K, Takami T, Yamabe H, Takano Y, Izumo T, Nagatani T, Mohri N, Nasu K, Satoh H, Katano H, Fujimoto J, Yamamoto T, Mori S.
Blood. 1995 Sep 1;86(5):1954-60.
PMID 7655022
 
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H.
Nature. 2007 Aug 2;448(7153):561-6. Epub 2007 Jul 11.
PMID 17625570
 
CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.
Stein H, Foss HD, Durkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B.
Blood. 2000 Dec 1;96(12):3681-95. (REVIEW)
PMID 11090048
 
Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types.
Stoica GE, Kuo A, Powers C, Bowden ET, Sale EB, Riegel AT, Wellstein A.
J Biol Chem. 2002 Sep 27;277(39):35990-8. Epub 2002 Jul 16.
PMID 12122009
 
KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer.
Takeuchi K, Choi YL, Togashi Y, Soda M, Hatano S, Inamura K, Takada S, Ueno T, Yamashita Y, Satoh Y, Okumura S, Nakagawa K, Ishikawa Y, Mano H.
Clin Cancer Res. 2009 May 1;15(9):3143-9. Epub 2009 Apr 21.
PMID 19383809
 
Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma.
Tort F, Pinyol M, Pulford K, Roncador G, Hernandez L, Nayach I, Kluin-Nelemans HC, Kluin P, Touriol C, Delsol G, Mason D, Campo E.
Lab Invest. 2001 Mar;81(3):419-26.
PMID 11310834
 
Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like).
Touriol C, Greenland C, Lamant L, Pulford K, Bernard F, Rousset T, Mason DY, Delsol G.
Blood. 2000 May 15;95(10):3204-7.
PMID 10807789
 
A new variant anaplastic lymphoma kinase (ALK)-fusion protein (ATIC-ALK) in a case of ALK-positive anaplastic large cell lymphoma.
Trinei M, Lanfrancone L, Campo E, Pulford K, Mason DY, Pelicci PG, Falini B.
Cancer Res. 2000 Feb 15;60(4):793-8.
PMID 10706082
 
What have we learnt from mouse models of NPM-ALK-induced lymphomagenesis?
Turner SD, Alexander DR.
Leukemia. 2005 Jul;19(7):1128-34. (REVIEW)
PMID 15902287
 
Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy.
Webb TR, Slavish J, George RE, Look AT, Xue L, Jiang Q, Cui X, Rentrop WB, Morris SW.
Expert Rev Anticancer Ther. 2009 Mar;9(3):331-56. (REVIEW)
PMID 19275511
 

Citation

This paper should be referenced as such :
Allouche, M
ALK (anaplastic lymphoma receptor tyrosine kinase)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(11):1059-1064.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ALKID16.html
History of this paper:
Huret, JL. ALK (anaplastic lymphoma kinase). Atlas Genet Cytogenet Oncol Haematol. 1997;1(1):4-4.
http://documents.irevues.inist.fr/bitstream/handle/2042/32020/09-1997-ALK.pdf
Huret, JL. ALK (anaplastic lymphoma kinase). Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):249-251.
http://documents.irevues.inist.fr/bitstream/handle/2042/37775/08-2001-ALK.pdf
Huret, JL ; Senon, S. ALK (anaplastic lymphoma kinase). Atlas Genet Cytogenet Oncol Haematol. 2003;7(4):216-219.
http://documents.irevues.inist.fr/bitstream/handle/2042/38004/08-2003-ALK.pdf

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 20 ]
  Anaplastic large cell lymphoma, ALK-negative
ALK -positive diffuse large B-cell lymphoma
Anaplastic large cell lymphoma (ALCL)
inv(2)(p23q13) RANBP2/ALK::t(2;2)(p23;q13) RANBP2/ALK
inv(2)(p23q35) ATIC/ALK
Primary cutaneous CD30+ anaplastic large cell lymphoma
t(1;2)(q25;p23) TPM3/ALK
t(2;3)(p23;q21) TFG/ALK
t(2;5)(p23;q35) NPM1/ALK
t(2;5)(p23;q35) SQSTM1/ALK
t(2;8)(q12;p11) RANBP2/FGFR1
t(2;9)(p23;q33) TRAF1/ALK
t(2;9)(q12;q34) RANBP2/ABL1
t(2;17)(p23;q23) CLTC/ALK
t(2;17)(p23;q25) RNF213/ALK
t(2;19)(p23;p13) TPM4/ALK
t(2;22)(p23;q11) CLTCL1/ALK
t(2;22)(p23;q11) MYH9/ALK
t(X;2)(q11;p23) MSN/ALK
Classification of T-Cell disorders

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 14 ]
  Kidney: ALK-rearranged renal cell carcinoma
Soft Tissues: Desmoid-type fibromatosis
Lung: Non-small cell carcinoma with inv(2)(p21p23) EML4/ALK
Soft Tissues: Inflammatory myofibroblastic tumor
Nervous system: Peripheral neuroblastic tumours (Neuroblastoma, Ganglioneuroblastoma, Ganglioneuroma)
Soft tissue tumors: an overview
Soft Tissues: Inflammatory myofibroblastic tumor with t(1;2)(q21;p23) TPM3/ALK
Soft Tissues: Inflammatory myofibroblastic tumor with t(2;2)(p23;q13) EWSR1/PBX1
Soft Tissues: Inflammatory myofibroblastic tumor with t(2;11)(p23;p15) CARS/ALK
Soft Tissues: Inflammatory myofibroblastic tumor with t(2;17)(p23;q23) CLTC/ALK
Soft Tissues: Inflammatory myofibroblastic tumor with t(2;19)(p23;p13) TPM4/ALK
Thyroid: Papillary carcinoma with inv(10)(p12.1q11.2) ACBD5/RET
Lung: Translocations in Adenocarcinoma
Lung: Translocations in Squamous Cell Carcinoma

External links

Nomenclature
HGNC (Hugo)ALK   427
LRG (Locus Reference Genomic)LRG_488
Cards
AtlasALKID16
Entrez_Gene (NCBI)ALK  238  ALK receptor tyrosine kinase
AliasesCD246; NBLST3
GeneCards (Weizmann)ALK
Ensembl hg19 (Hinxton)ENSG00000171094 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000171094 [Gene_View]  chr2:29192774-29921611 [Contig_View]  ALK [Vega]
ICGC DataPortalENSG00000171094
TCGA cBioPortalALK
AceView (NCBI)ALK
Genatlas (Paris)ALK
WikiGenes238
SOURCE (Princeton)ALK
Genetics Home Reference (NIH)ALK
Genomic and cartography
GoldenPath hg38 (UCSC)ALK  -     chr2:29192774-29921611 -  2p23.2-p23.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ALK  -     2p23.2-p23.1   [Description]    (hg19-Feb_2009)
EnsemblALK - 2p23.2-p23.1 [CytoView hg19]  ALK - 2p23.2-p23.1 [CytoView hg38]
Mapping of homologs : NCBIALK [Mapview hg19]  ALK [Mapview hg38]
OMIM105590   613014   
Gene and transcription
Genbank (Entrez)AB209477 AK296218 BC156207 BC157090 DA455128
RefSeq transcript (Entrez)NM_004304
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ALK
Cluster EST : UnigeneHs.654469 [ NCBI ]
CGAP (NCI)Hs.654469
Alternative Splicing GalleryENSG00000171094
Gene ExpressionALK [ NCBI-GEO ]   ALK [ EBI - ARRAY_EXPRESS ]   ALK [ SEEK ]   ALK [ MEM ]
Gene Expression Viewer (FireBrowse)ALK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)238
GTEX Portal (Tissue expression)ALK
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UM73   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UM73  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UM73
Splice isoforms : SwissVarQ9UM73
Catalytic activity : Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.12.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   
PhosPhoSitePlusQ9UM73
Domaine pattern : Prosite (Expaxy)MAM_2 (PS50060)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)    RECEPTOR_TYR_KIN_II (PS00239)   
Domains : Interpro (EBI)ALK    ConA-like_dom    Kinase-like_dom    LDrepeatLR_classA_rpt    MAM_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kinase_AS    Tyr_kinase_cat_dom    Tyr_kinase_rcpt_2_CS   
Domain families : Pfam (Sanger)MAM (PF00629)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam00629    pfam07714   
Domain families : Smart (EMBL)LDLa (SM00192)  TyrKc (SM00219)  
Conserved Domain (NCBI)ALK
DMDM Disease mutations238
Blocks (Seattle)ALK
PDB (SRS)###############################################################################################################################################################################################################################################################   
PDB (PDBSum)###############################################################################################################################################################################################################################################################   
PDB (IMB)###############################################################################################################################################################################################################################################################   
PDB (RSDB)###############################################################################################################################################################################################################################################################   
Structural Biology KnowledgeBase###############################################################################################################################################################################################################################################################   
SCOP (Structural Classification of Proteins)###############################################################################################################################################################################################################################################################   
CATH (Classification of proteins structures)###############################################################################################################################################################################################################################################################   
SuperfamilyQ9UM73
Human Protein AtlasENSG00000171094
Peptide AtlasQ9UM73
HPRD00104
IPIIPI00395632   IPI00930494   IPI00910903   IPI00893651   
Protein Interaction databases
DIP (DOE-UCLA)Q9UM73
IntAct (EBI)Q9UM73
FunCoupENSG00000171094
BioGRIDALK
STRING (EMBL)ALK
ZODIACALK
Ontologies - Pathways
QuickGOQ9UM73
Ontology : AmiGOactivation of MAPK activity  NF-kappaB-inducing kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  protein binding  ATP binding  intracellular  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  signal transduction  transmembrane receptor protein tyrosine kinase signaling pathway  cell proliferation  phosphorylation  phosphorylation  peptidyl-tyrosine phosphorylation  hippocampus development  adult behavior  swimming behavior  NIK/NF-kappaB signaling  regulation of cell proliferation  identical protein binding  regulation of apoptotic process  protein complex  protein autophosphorylation  protein autophosphorylation  neuron development  positive regulation of NF-kappaB transcription factor activity  regulation of dopamine receptor signaling pathway  extracellular exosome  response to environmental enrichment  
Ontology : EGO-EBIactivation of MAPK activity  NF-kappaB-inducing kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  protein binding  ATP binding  intracellular  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  signal transduction  transmembrane receptor protein tyrosine kinase signaling pathway  cell proliferation  phosphorylation  phosphorylation  peptidyl-tyrosine phosphorylation  hippocampus development  adult behavior  swimming behavior  NIK/NF-kappaB signaling  regulation of cell proliferation  identical protein binding  regulation of apoptotic process  protein complex  protein autophosphorylation  protein autophosphorylation  neuron development  positive regulation of NF-kappaB transcription factor activity  regulation of dopamine receptor signaling pathway  extracellular exosome  response to environmental enrichment  
Pathways : KEGGNon-small cell lung cancer   
NDEx NetworkALK
Atlas of Cancer Signalling NetworkALK
Wikipedia pathwaysALK
Orthology - Evolution
OrthoDB238
GeneTree (enSembl)ENSG00000171094
Phylogenetic Trees/Animal Genes : TreeFamALK
HOVERGENQ9UM73
HOGENOMQ9UM73
Homologs : HomoloGeneALK
Homology/Alignments : Family Browser (UCSC)ALK
Gene fusions - Rearrangements
Fusion : MitelmanA2M/ALK [12p13.31/2p23.2]  [t(2;12)(p23;p13)]  
Fusion : MitelmanALK/PTPN3 [2p23.2/9q31.3]  [t(2;9)(p23;q31)]  
Fusion : MitelmanATIC/ALK [2q35/2p23.2]  [inv(2)(p23q35)]  
Fusion : MitelmanC2orf44/ALK [2p23.3/2p23.2]  [dup(2)(p23p24)]  
Fusion : MitelmanC2orf61/ALK [2p21/2p23.2]  [t(2;2)(p21;p23)]  
Fusion : MitelmanCARS/ALK [11p15.4/2p23.2]  [t(2;11)(p23;p15)]  
Fusion : MitelmanCLTCL1/ALK [22q11.21/2p23.2]  [t(2;22)(p23;q11)]  
Fusion : MitelmanCLTC/ALK [17q23.1/2p23.2]  [t(2;17)(p23;q23)]  
Fusion : MitelmanEML4/ALK [2p21/2p23.2]  [del(2)(p21p23)]  [inv(2)(p21p23)]  
[t(2;2)(p21;p23)]  
Fusion : MitelmanFN1/ALK [2q35/2p23.2]  [t(2;2)(p23;q35)]  
Fusion : MitelmanGTF2IRD1/ALK [7q11.23/2p23.2]  [t(2;7)(p23;q11)]  
Fusion : MitelmanHIP1/ALK [7q11.23/2p23.2]  [t(2;7)(p23;q11)]  
Fusion : MitelmanKCNQ5/ALK [6q13/2p23.2]  [t(2;6)(p23;q13)]  
Fusion : MitelmanKIF5B/ALK [10p11.22/2p23.2]  [t(2;10)(p23;p11)]  
Fusion : MitelmanKLC1/ALK [14q32.33/2p23.2]  [t(2;14)(p23;q32)]  
Fusion : MitelmanLMNA/ALK [1q22/2p23.2]  [t(1;2)(q22;p23)]  
Fusion : MitelmanMALAT1/ALK [11q13.1/2p23.2]  [t(2;11)(p23;q13)]  
Fusion : MitelmanMSN/ALK [Xq12/2p23.2]  [t(X;2)(q11;p23)]  
Fusion : MitelmanMYH9/ALK [22q12.3/2p23.2]  [t(2;22)(p23;q12)]  
Fusion : MitelmanNPM1/ALK [5q35.1/2p23.2]  [ins(5;2)(q35;p23p23)]  [t(2;5)(p23;q35)]  
Fusion : MitelmanPPFIBP1/ALK [12p11.23/2p23.2]  [t(2;12)(p23;p11)]  
Fusion : MitelmanPRKAR1A/ALK [17q24.2/2p23.2]  [t(2;17)(p23;q24)]  
Fusion : MitelmanRANBP2/ALK [2q12.3/2p23.2]  [inv(2)(p23q13)]  [t(2;2)(p23;q13)]  
Fusion : MitelmanRNF213/ALK [17q25.3/2p23.2]  [t(2;17)(p23;q25)]  
Fusion : MitelmanSEC31A/ALK [4q21.22/2p23.2]  [t(2;4)(p23;q21)]  
Fusion : MitelmanSQSTM1/ALK [5q35.3/2p23.2]  [t(2;5)(p23;q35)]  
Fusion : MitelmanSTRN/ALK [2p22.2/2p23.2]  [del(2)(p22p23)]  [t(2;2)(p22;p23)]  
Fusion : MitelmanTFG/ALK [3q12.2/2p23.2]  [t(2;3)(p23;q12)]  
Fusion : MitelmanTPM1/ALK [15q22.2/2p23.2]  [t(2;15)(p23;q22)]  
Fusion : MitelmanTPM3/ALK [1q21.3/2p23.2]  [t(1;2)(q21;p23)]  
Fusion : MitelmanTPM4/ALK [19p13.12/2p23.2]  [t(2;19)(p23;p13)]  
Fusion : MitelmanTPR/ALK [1q31.1/2p23.2]  [t(1;2)(q31;p23)]  
Fusion : MitelmanTRAF1/ALK [9q33.2/2p23.2]  [t(2;9)(p23;q33)]  
Fusion : MitelmanVCL/ALK [10q22.2/2p23.2]  [t(2;10)(p23;q22)]  
Fusion : COSMICALK [2p23.2]  -  MSN [Xq12]  [fusion_423]  [fusion_468]  
Fusion : COSMICATIC [2q35]  -  ALK [2p23.2]  [fusion_444]  [fusion_445]  [fusion_446]  
Fusion : COSMICC2orf44 [ALK]  -  2p23.2 [1264]  [fusion_1282]  
Fusion : COSMICCARS [11p15.4]  -  ALK [2p23.2]  [fusion_437]  [fusion_438]  [fusion_753]  
Fusion : COSMICCLTC [17q23.1]  -  ALK [2p23.2]  [fusion_434]  [fusion_435]  [fusion_436]  [fusion_469]  [fusion_470]  [fusion_472]  
Fusion : COSMICDCTN1 [2p13.1]  -  ALK [2p23.2]  [fusion_1616]  [fusion_1617]  [fusion_1625]  [fusion_1626]  
Fusion : COSMICEML4 [2p21]  -  ALK [2p23.2]  [fusion_1062]  [fusion_1063]  [fusion_1064]  [fusion_1065]  [fusion_1127]  [fusion_1128]  [fusion_1296]  
[fusion_1297]  [fusion_1368]  [fusion_1376]  [fusion_1539]  [fusion_1540]  [fusion_1541]  [fusion_1542]  [fusion_1543]  [fusion_1544]  [fusion_1545]  
[fusion_408]  [fusion_409]  [fusion_410]  [fusion_411]  [fusion_413]  [fusion_414]  [fusion_462]  [fusion_463]  [fusion_464]  [fusion_465]  
[fusion_473]  [fusion_474]  [fusion_475]  [fusion_476]  [fusion_477]  [fusion_478]  [fusion_479]  [fusion_480]  [fusion_487]  [fusion_488]  
[fusion_489]  [fusion_490]  [fusion_491]  [fusion_493]  [fusion_730]  [fusion_731]  [fusion_732]  [fusion_733]  [fusion_734]  
Fusion : COSMICFN1 [2q35]  -  ALK [2p23.2]  [fusion_1300]  [fusion_1301]  
Fusion : COSMICHIP1 [7q11.23]  -  ALK [2p23.2]  [fusion_1614]  [fusion_1615]  [fusion_1620]  [fusion_1621]  [fusion_1712]  [fusion_1713]  
Fusion : COSMICKIF5B [10p11.22]  -  ALK [2p23.2]  [fusion_1058]  [fusion_1059]  [fusion_1060]  [fusion_1061]  [fusion_1257]  [fusion_1258]  [fusion_1381]  
[fusion_1382]  [fusion_1485]  
Fusion : COSMICKLC1 [14q32.33]  -  ALK [2p23.2]  [fusion_1276]  [fusion_1277]  
Fusion : COSMICMSN [Xq12]  -  ALK [2p23.2]  [fusion_421]  [fusion_422]  [fusion_467]  
Fusion : COSMICNPM1 [5q35.1]  -  ALK [2p23.2]  [fusion_198]  [fusion_199]  [fusion_200]  [fusion_201]  [fusion_420]  [fusion_448]  [fusion_449]  
[fusion_450]  [fusion_451]  [fusion_452]  [fusion_453]  [fusion_454]  [fusion_455]  [fusion_456]  [fusion_457]  [fusion_458]  
Fusion : COSMICPPFIBP1 [12p11.23]  -  ALK [2p23.2]  [fusion_1054]  [fusion_1055]  [fusion_1461]  [fusion_1462]  
Fusion : COSMICRANBP2 [2q13]  -  ALK [2p23.2]  [fusion_415]  [fusion_416]  [fusion_417]  [fusion_418]  
Fusion : COSMICSEC31A [4q21.22]  -  ALK [2p23.2]  [fusion_459]  [fusion_460]  [fusion_461]  
Fusion : COSMICSQSTM1 [5q35.3]  -  ALK [2p23.2]  [fusion_1051]  [fusion_1052]  
Fusion : COSMICSTRN [2p22.2]  -  ALK [2p23.2]  [fusion_1430]  [fusion_1431]  [fusion_1538]  [fusion_1669]  [fusion_1670]  
Fusion : COSMICTFG [3q12.2]  -  ALK [2p23.2]  [fusion_424]  [fusion_425]  [fusion_426]  [fusion_428]  [fusion_429]  [fusion_430]  [fusion_432]  
[fusion_433]  
Fusion : COSMICTPM3 [1q21.3]  -  ALK [2p23.2]  [fusion_439]  [fusion_440]  [fusion_443]  
Fusion : COSMICTPM4 [19p13.12]  -  ALK [2p23.2]  [fusion_441]  [fusion_442]  
Fusion : COSMICVCL [10q22.2]  -  ALK [2p23.2]  [fusion_1056]  [fusion_1057]  
Fusion: TCGAC2orf61 2p21 ALK 2p23.2 OV
Fusion: TCGAEML4 2p21 ALK 2p23.2 LUAD THCA
Fusion: TCGAGTF2IRD1 7q11.23 ALK 2p23.2 THCA
Fusion: TCGAKCNQ5 6q13 ALK 2p23.2 SKCM
Fusion: TCGASTRN 2p22.2 ALK 2p23.2 THCA
Fusion: TCGATPM1 15q22.2 ALK 2p23.2 BLCA
Fusion : TICdbALK [2p23.2]  -  PTPN3 [9q31.3]
Fusion : TICdbATIC [2q35]  -  ALK [2p23.2]
Fusion : TICdbCARS [11p15.4]  -  ALK [2p23.2]
Fusion : TICdbCLTC [17q23.1]  -  ALK [2p23.2]
Fusion : TICdbEML4 [2p21]  -  ALK [2p23.2]
Fusion : TICdbKIF5B [10p11.22]  -  ALK [2p23.2]
Fusion : TICdbMSN [Xq12]  -  ALK [2p23.2]
Fusion : TICdbMYH9 [22q12.3]  -  ALK [2p23.2]
Fusion : TICdbNPM1 [5q35.1]  -  ALK [2p23.2]
Fusion : TICdbRANBP2 [2q12.3]  -  ALK [2p23.2]
Fusion : TICdbRNF213 [17q25.3]  -  ALK [2p23.2]
Fusion : TICdbSEC31A [4q21.22]  -  ALK [2p23.2]
Fusion : TICdbSQSTM1 [5q35.3]  -  ALK [2p23.2]
Fusion : TICdbTFG [3q12.2]  -  ALK [2p23.2]
Fusion : TICdbTPM3 [1q21.3]  -  ALK [2p23.2]
Fusion : TICdbTPM4 [19p13.12]  -  ALK [2p23.2]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerALK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ALK
dbVarALK
ClinVarALK
1000_GenomesALK 
Exome Variant ServerALK
ExAC (Exome Aggregation Consortium)ALK (select the gene name)
Genetic variants : HAPMAP238
Genomic Variants (DGV)ALK [DGVbeta]
DECIPHERALK [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisALK 
Mutations
ICGC Data PortalALK 
TCGA Data PortalALK 
Broad Tumor PortalALK
OASIS PortalALK [ Somatic mutations - Copy number]
Cancer Gene: CensusALK 
Somatic Mutations in Cancer : COSMICALK  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDALK
intOGen PortalALK
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Mendelian genes
BioMutasearch ALK
DgiDB (Drug Gene Interaction Database)ALK
DoCM (Curated mutations)ALK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ALK (select a term)
intoGenALK
NCG5 (London)ALK
Cancer3DALK(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM105590    613014   
Orphanet548    548    18017    905    22363    22213    21151   
MedgenALK
Genetic Testing Registry ALK
NextProtQ9UM73 [Medical]
TSGene238
GENETestsALK
Target ValidationALK
Huge Navigator ALK [HugePedia]
snp3D : Map Gene to Disease238
BioCentury BCIQALK
ClinGenALK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD238
Chemical/Pharm GKB GenePA24719
Clinical trialALK
Miscellaneous
canSAR (ICR)ALK (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=ALK
Probes
Litterature
PubMed477 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineALK
EVEXALK
GoPubMedALK
iHOPALK
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 Jun 30 11:00:36 CEST 2017
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.