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t(2;3)(p23;q21) TFG/ALK

Written2001-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 1217
 
  t(2;3)(p23;q21) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.

Clinics and Pathology

Disease
  • Anaplasic large cell lymphoma: translocations involving 2p23 are found in more than half cases of anaplasic large cell lymphoma (ALCL), a high grade non Hodgkin lymphoma (NHL). They involve ALK, and are therefore called ALK+ ALCL.
  • The most frequent ALK+ ALCL being the the t(2;5)(p23;q35) with NPM1 -ALK fusion protein, which localises both in the cytoplasm and in the nucleus.
  • The t(2;3)(p23;q21) is very rare., and, like other t(2;Var) involving various partners and ALK, the fusion protein has a cytoplasmic localization; they are therefore called "cytoplasm only" ALK+ ALCL.
    • Epidemiology only 2 cases to date: a 10 yr old girl and a 19 yr old man.
    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 t(2;3) cases.

    Genes involved and Proteins

    Gene NameALK (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 NameTFG (TRK-fused gene)
    Location 3q12.2
    Protein 406 amino acids, 44 kDa; widely expressed
    Somatic mutations apart from the TFG-ALK herein described (see below), TFG is also known to de fused to NTRK1ID: 216> in a subset of

    Result of the chromosomal anomaly

    Hybrid gene
    Description 5' TFG - 3' ALK
      
    Fusion Protein
    Description 83 kDa and 96-97 kDa; as the breakpoint in TPM3 was variable , 701 amino acids in the sort er fusion protein, composed of 138 N-term amino acids from TFG, including the cioled-coil oligomerization domain fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain); homodimerization of the fusion protein.
    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).
      

    To be noted

    Additional cases are needed to delineate the epidemiology of this rare entity:
    you are welcome to submit a paper to our new Case Report section.

    Bibliography

    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
     
    TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.
    Hernández L, Pinyol M, Hernández S, Beá S, Pulford K, Rosenwald A, Lamant L, Falini B, Ott G, Mason DY, Delsol G, Campo E
    Blood. 1999 ; 94 (9) : 3265-3268.
    PMID 10556217
     
    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
     
    t(1;2)(q21;p23) and t(2;3)(p23;q21): two novel variant translocations of the t(2;5)(p23;q35) in anaplastic large cell lymphoma.
    Rosenwald A, Ott G, Pulford K, Katzenberger T, Kühl J, Kalla J, Ott MM, Mason DY, Müller-Hermelink HK
    Blood. 1999 ; 94 (1) : 362-364.
    PMID 10381534
     
    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
     

    Citation

    This paper should be referenced as such :
    Huret, JL
    t(2;3)(p23;q21)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):281-282.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/t0203ID1217.html

    Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

    Genes ALK TFG

    Translocations implicated (Data extracted from papers in the Atlas)

     t(2;3)(p23;q21) TFG/ALK

    External links

    TFG (3q12.2) ALK (2p23.2)

    TFG (3q12.2) ALK (2p23.2)

    Mitelman databaset(2;3)(p23;q21)
    arrayMap (UZH-SIB Zurich)[select an item]
     
    Mitelman databaseTFG/ALK [MCList]  TFG (3q12.2) ALK (2p23.2)
    TICdbTFG/ALK  TFG (3q12.2) ALK (2p23.2)
     
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed


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