| Written | 2001-08 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| Atlas_Id | 1172 |
| Clinics and Pathology |
| Disease | |
| Phenotype / cell stem origin | CD30+; ALK+ |
| Epidemiology | at least 7 known cases, aged 12 yrs to 52 yrs (med 23 yrs); no sex unbalance so far, in contrast with the general feature found in ALK+ ALCL |
| Clinics | ALK+ ALCL without the t(2;5) (so called cytoplasmic only ALK cases) show clinical features similar to those of classical ALK+ ALCL: young age, male predominance, presentation with advanced disease, systemic symptoms, frequent involvement of extranodal sites, and a good prognosis. Nothing in particular is known concerning inv(2) cases, as cases are not fully documented |
| Prognosis | not well documented |
| Cytogenetics |
| Cytogenetics Morphological | difficult to identify, as breakpoints lie in telomeric regions; an apparent i(2q) -when present- in ALCL should ring the bell; in some other cases, with numerous anomalies, there is no apparent breakpoint on chromosomes 2. |
| Cytogenetics Molecular | FISH analyses are thereof essential |
| Additional anomalies | ider(2)(q10)inv(2) has been found in some cases, carrying 2 additional copies of the ATIC-ALK hybrid gene, as detected with FISH; frequent complex karyotypes |
| Genes involved and Proteins |
| Gene Name | ALK (anaplastic lymphoma receptor tyrosine kinase) |
| Location | 2p23.2 |
| Protein | 1620 amino acids; 177 kDa; glycoprotein (200 kDa mature protein) ; membrane associated tyrosine kinase receptor |
| Gene Name | ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) |
| Location | 2q35 |
| Protein | 591 amino acids, 64 kDa; bifunctional purine biosythesis:9th and 10th step of the de novo purine synthesis |
| Result of the chromosomal anomaly |
| Description | 5' ATIC- 3' ALK |
| Description | 791 amino acids, 87 kDa. 229 N-term amino acid from ATIC containing the IMPCH domain and the dimerization domain fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain). |
| Expression Localisation | cytoplasmic localisation (in contrast with the t(2;5)(p23;q35) with NPM1-ALK, which localizes both in the cytoplasm and in the nucleus). |
| Oncogenesis | ATIC seems to provoke the dimerization of ATIC-ALK, which should lead to constitutive autophosphorylation and activation of the ALK tyrosine kinase, as for NPM1-ALK (see t(2;5)(p23;q35) ) |
| Bibliography |
| 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 |
| The American journal of pathology. 2000 ; 156 (3) : 781-789. |
| PMID 10702393 |
| Anaplastic large cell lymphomas, Primary systemic (T/Null cell type). |
| Delsol G, Ralfkiaer E, Stein H, Wright D, Jaffe E |
| World Health Organization (WHO) Classification of Tumors.. |
| 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 : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (9) : 1533-1559. |
| PMID 10994999 |
| Lymphomas expressing ALK fusion protein(s) other than NPM-ALK. |
| Falini B, Pulford K, Pucciarini A, Carbone A, De Wolf-Peeters C, Cordell J, Fizzotti M, Santucci A, Pelicci PG, Pileri S, Campo E, Ott G, Delsol G, Mason DY |
| Blood. 1999 ; 94 (10) : 3509-3515. |
| PMID 10552961 |
| 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 ; 14 (4) : 439-449. |
| PMID 9053841 |
| 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 ; 95 (6) : 2144-2149. |
| PMID 10706887 |
| Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma. |
| Morris SW, Xue L, Ma Z, Kinney MC |
| British journal of haematology. 2001 ; 113 (2) : 275-295. |
| PMID 11380391 |
| CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. |
| Stein H, Foss HD, Dürkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B |
| Blood. 2000 ; 96 (12) : 3681-3695. |
| PMID 11090048 |
| 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 research. 2000 ; 60 (4) : 793-798. |
| PMID 10706082 |
| The cryptic inv(2)(p23q35) defines a new molecular genetic subtype of ALK-positive anaplastic large-cell lymphoma. |
| Wlodarska I, De Wolf-Peeters C, Falini B, Verhoef G, Morris SW, Hagemeijer A, Van den Berghe H |
| Blood. 1998 ; 92 (8) : 2688-2695. |
| PMID 9763551 |
| Citation |
| This paper should be referenced as such : |
| Huret, JL |
| inv(2)(p23q35) |
| Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):277-278. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/inv2p23q35ID1172.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 3 ] |
| Genes | ALK | ALK | ATIC |
| Translocations implicated (Data extracted from papers in the Atlas) |
| inv(2)(p23q35) ATIC/ALK | |
| External links |
| Mitelman database | inv(2)(p23q35) |
| arrayMap (UZH-SIB Zurich) | [select an item] |
| COSMIC_fusion | ATIC/ALK ATIC (2q35) ALK (2p23.2) [fusion444] [fusion445] [fusion446] |
| Mitelman database | ATIC::ALK [MCList] ATIC (2q35) ALK (2p23.2) |
| Mitelman database | ATIC::ALK [MCList] ATIC (2q35) ALK (2p23.2) |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Oct 8 16:35:41 CEST 2021 |
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