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

2001-08-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


  • 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.


    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 name
    ALK (anaplastic lymphoma receptor tyrosine kinase)
    Protein description
    1620 amino acids; 177 kDa; glycoprotein (200 kDa mature protein) ; membrane associated tyrosine kinase receptor
    Gene name
    TFG (TRK-fused gene)
    Protein description
    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


    5 TFG - 3 ALK83 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).

    Highly cited references

    Pubmed IDYearTitleCitations
    121125242002Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.65
    105562171999TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.58
    182427622008EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas.55
    152086562004Differential effects of X-ALK fusion proteins on proliferation, transformation, and invasion properties of NIH3T3 cells.45
    109949992000Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.43
    108077892000Further 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).38
    198884732009Intrinsic structural disorder confers cellular viability on oncogenic fusion proteins.31
    278741932017ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma.23
    119437322002Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity.23
    251482362014Identification of oncogenic mutations and gene fusions in the follicular variant of papillary thyroid carcinoma.22
    285494582017Detection of ALK fusion transcripts in FFPE lung cancer samples by NanoString technology.12
    347271722022ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.5
    315219782019The clinical responses of TNIP2-ALK fusion variants to crizotinib in ALK-rearranged lung adenocarcinoma.5
    337316902021Non-secretory multiple myeloma with unusual TFG-ALK fusion showed dramatic response to ALK inhibition.1
    146318062003[Anaplastic large-cell lymphoma: review].0


    Pubmed IDLast YearTitleAuthors
    109949992000Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.Drexler HG et al
    105562171999TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.Hernández L et al
    113803912001Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Morris SW et al
    103815341999t(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 et al
    110900482000CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.Stein H et al


    Fusion gene

    TFG/ALK TFG (3q12.2) ALK (2p23.2) M t(2;3)(p23;q12)|TFG/ALK TFG (3q12.2) ALK (2p23.2) TIC
    Atlas Image
    t(2;3)(p23;q21) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.


    Jean-Loup Huret

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

    Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

    Online version: http://atlasgeneticsoncology.org/haematological/1217/t(2;3)(p23;q21)