t(1;2)(q25;p23) TPM3/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.Inflammatory myofibroblastic tumors
  • The t(1;2)(q25;p23) 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

    a very few (four) cases known so far


    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(1;2) cases, as cases are not documented.


    complex karyotypes and/or hidden translocation in the 2 cases with cytogenetic data; FISH analyses are essential


    rare soft tissue tumour found in children and young adults


    spindle cell proliferation with myofibroblastic differenciation and an inflammatory infiltrate


    low malignant potential and good prognosis

    Genes Involved and Proteins

    Gene name
    TPM3 (tropomyosin 3)
    Protein description
    284 amino acids, 33 kDa; coiled coil structure; role in Calcium dependant actin-myosin interaction
    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

    Result of the Chromosomal Anomaly


    5 TPM3 - 3 ALK104 kDa ; 221 (?) N-term amino acids from TPM3 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).


    TPM3-ALK is contituvely activated


    Pubmed IDLast YearTitleAuthors
    109949992000Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.Drexler HG et al
    103831291999Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.Griffin CA et al
    109341372000Aberrant ALK tyrosine kinase signaling. Different cellular lineages, common oncogenic mechanisms.Ladanyi M et al
    102161061999A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation.Lamant L et al
    109341422000TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.Lawrence B et al
    113803912001Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Morris SW et al
    106101191999Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma.Siebert R et al
    110900482000CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.Stein H et al


    Fusion gene

    TPM3/ALK TPM3 (1q21.3) ALK (2p23.2) M t(1;2)(q21;p23)|TPM3/ALK TPM3 (1q21.3) ALK (2p23.2) TIC


    Jean-Loup Huret

    t(1;2)(q25;p23) TPM3/ALK

    Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

    Online version: http://atlasgeneticsoncology.org/haematological/1168/t(1;2)(q25;p23)

    External Links