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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)


Other aliasanaplastic lymphoma kinase (Ki-1)
LocusID (NCBI) 238
Atlas_Id 16
Location 2p23.2  [Link to chromosome band 2p23]
Location_base_pair Starts at and ends at bp from pter
  ALK (2p23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
  ALK (anaplastic lymphoma receptor tyrosine kinase) Hybridization with Vysis ALK Break Apart probe (Abbott Molecular, US) showing the gene at 2p23 (red-green or a fused yellow signal - Courtesy Adriana Zamecnikova.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
A2M (12p13.31) / ALK (2p23.2)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) / GALNT17 (7q11.22)
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)BIRC6 (2p22.3) / ALK (2p23.2)
CAD (2p23.3) / ALK (2p23.2)CARS (11p15.4) / ALK (2p23.2)CCDC88A (2p16.1) / 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)GFPT1 (2p13.3) / ALK (2p23.2)GTF2IRD1 (7q11.23) / ALK (2p23.2)
HIP1 (7q11.23) / ALK (2p23.2)HOOK1 (1p32.1) / ALK (2p23.2)KCNQ5 (6q13) / ALK (2p23.2)
KIF5B (10p11.22) / ALK (2p23.2)KLC1 (14q32.33) / ALK (2p23.2)KTN1 (14q22.3) / 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)
RANBP2 (2q13) / ALK (2p23.2)RNF213 (17q25.3) / ALK (2p23.2)SEC31A (4q21.22) / ALK (2p23.2)
SQSTM1 (5q35.3) / ALK (2p23.2)STPG4 (2p21) / 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)
WDCP (2p23.3) / ALK (2p23.2)


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


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

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.


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).


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
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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
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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
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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.
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J Biol Chem. 2002 Sep 27;277(39):35990-8. Epub 2002 Jul 16.
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KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer.
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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).
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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 :
History of this paper:
Huret, JL. ALK (anaplastic lymphoma kinase). Atlas Genet Cytogenet Oncol Haematol. 1997;1(1):4-4.
Huret, JL. ALK (anaplastic lymphoma kinase). Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):249-251.
Huret, JL ; Senon, S. ALK (anaplastic lymphoma kinase). Atlas Genet Cytogenet Oncol Haematol. 2003;7(4):216-219.

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 44 ]
  Anaplastic large cell lymphoma (ALCL)
inv(2)(p23q35) ATIC/ALK
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;9)(p23;q33) TRAF1/ALK
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
inv(2)(p21p23) EML4/ALK
t(1;2)(q21;p23) TPM3/ALK
inv(2)(p23q13)|t(2;2)(p23;q13) RANBP2/ALK
t(2;3)(p23;q12) TFG/ALK
t(2;4)(p23;q21) SEC31A/ALK
t(2;22)(p23;q12) MYH9/ALK
Anaplastic large cell lymphoma, ALK-negative
ALK -positive diffuse large B-cell lymphoma
Anaplastic large cell lymphoma (ALCL)
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
inv(2)(p21p23) EML4/ALK
t(1;2)(q21;p23) TPM3/ALK
inv(2)(p23q13)|t(2;2)(p23;q13) RANBP2/ALK
t(2;3)(p23;q12) TFG/ALK
t(2;4)(p23;q21) SEC31A/ALK
t(2;22)(p23;q12) MYH9/ALK

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 52 ]
  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
del(2)(p16p23) CCDC88A/ALK
inv(2)(p21p23) EML4/ALK
inv(2)(p23q35) FN1/ALK
t(1;2)(q22;p23) LMNA/ALK
t(1;2)(q31;p23) TPR/ALK
t(1;2)(q41;p23) CENPF/ALK
t(2;2)(p13;p23) DCTN1/ALK
t(2;2)(p13;p23) DCTN1/ALK
t(2;2)(p13;p23) GFPT1/ALK
t(2;2)(p16;p23) PPP1R21/ALK
t(2;2)(p22;p23) BIRC6/ALK
CAD/ALK (2p23)
MAPRE3/ALK (2p23)
t(2;2)(p23;q12) GCC2/ALK
t(2;2)(p23;q35) FN1/ALK
t(2;2)(p23;q35) FN1/ALK
t(2;2)(p23;q35) FN1/ALK
t(2;2)(p23;q35) IGFBP5/ALK
t(2;5)(p23;q35) SQSTM1/ALK
t(2;5)(p23;q35) SQSTM1/ALK
t(2;6)(p23;p24) PHACTR1/ALK
t(2;6)(p23;q13) KCNQ5/ALK
t(2;7)(p23;p22) PRKAR1B/ALK
t(2;7)(p23;q11) GTF2IRD1/ALK
t(2;7)(p23;q11) GTF2IRD1/ALK
t(2;7)(p23;q11) HIP1/ALK
t(2;9)(p23;q31) ALK/PTPN3
t(2;11)(p23;q13) MALAT1/ALK
t(2;12)(p23;p13) A2M/ALK
t(2;12)(p23;q13) HNRNPA1/ALK
t(2;13)(p23;q22) LMO7/ALK
t(2;14)(p23;q22) KTN1/ALK
t(2;14)(p23;q32) KLC1/ALK
t(2;15)(p23;q14) THBS1/ALK
t(2;15)(p23;q22) TPM1/ALK
t(2;17)(p23;q24) PRKAR1A/ALK
t(2;22)(p23;q12) MYH9/ALK
t(2;22)(p23;q12) TIMP3/ALK

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)238
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
Other database
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 18 17:28:05 CEST 2018

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