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

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.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

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

    Cytogenetics

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

    Clinics

    rare soft tissue tumour found in children and young adults

    Pathology

    spindle cell proliferation with myofibroblastic differenciation and an inflammatory infiltrate

    Prognosis

    low malignant potential and good prognosis

    Genes Involved and Proteins

    Gene name
    TPM3 (tropomyosin 3)
    Location
    1q21.3
    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)
    Location
    2p23.2
    Protein description
    1620 amino acids; 177 kDa; glycoprotein (200 kDa mature protein) ; membrane associated tyrosine kinase receptor

    Result of the Chromosomal Anomaly

    Description

    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).

    Oncogenesis

    TPM3-ALK is contituvely activated

    Highly cited references

    Pubmed IDYearTitleCitations
    109341422000TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.145
    102161061999A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation.67
    217789992011Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas.46
    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
    222529912012Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method.38
    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
    107023932000ATIC-ALK: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35).36
    278741932017ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma.23
    277426572016Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib.23
    195452842009Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular-histological correlation.21
    186603802008ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy.20
    172760532007TPM3-ALK expression induces changes in cytoskeleton organisation and confers higher metastatic capacities than other ALK fusion proteins.15
    286593372017Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene.14
    281819502017Clinicopathologic and Molecular Pathology of Collecting Duct Carcinoma and Related Renal Cell Carcinomas.14
    267734392016ALK-rearranged renal cell carcinomas in children.14
    202239222010Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia.13
    281997422017Genetic analysis and clinicopathological features of ALK-rearranged renal cell carcinoma in a large series of resected Chinese renal cell carcinoma patients and literature review.12
    274506572016TFE3-positive renal cell carcinomas are not always Xp11 translocation carcinomas: Report of a case with a TPM3-ALK translocation.9
    166515372006Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins.8
    106101191999Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma.8
    255961292015Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3.6
    347271722022ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.5
    176607122007Development of a conditional bioluminescent transplant model for TPM3-ALK-induced tumorigenesis as a tool to validate ALK-dependent cancer targeted therapy.5
    157645782004Low-grade sarcomas with CD34-positive fibroblasts and low-grade myofibroblastic sarcomas.5
    225916832012ALK-positive anaplastic large cell lymphoma with TPM3-ALK translocation.4
    208706602010Malignant high-grade histological transformation of inflammatory myofibroblastic tumour associated with amplification of TPM3-ALK.4
    177202432008Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma.4
    169846142006Absence of human herpesvirus-8 and Epstein-Barr virus in inflammatory myofibroblastic tumor with anaplastic large cell lymphoma kinase fusion gene.4
    340016952021Clinicopathologic and Genomic Characterization of Inflammatory Myofibroblastic Tumors of the Head and Neck: Highlighting a Novel Fusion and Potential Diagnostic Pitfall.3
    254162342015Aggressive transformation of anaplastic large cell lymphoma with increased number of ALK-translocated chromosomes.3
    170633372007A case of an inflammatory myofibroblastic tumor in the lung which expressed TPM3-ALK gene fusion.2
    330919682021A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation.1
    316874672019Corresponding anaplastic lymphoma kinase-tropomyosin 3 (ALK-TPM3) fusion in a patient with a primary cutaneous anaplastic large-cell lymphoma and a Spitz nevus.1
    321021282020Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion.1
    127873122003Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype.1
    146318062003[Anaplastic large-cell lymphoma: review].0

    Article Bibliography

    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

    Summary

    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

    Citation

    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/gene-fusions-explorer/css/cancer-prone-explorer/