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Soft Tissues: Inflammatory myofibroblastic tumor with t(1;2)(q21;p23) TPM3/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 C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 8825/1 Inflammatory myofibroblastic tumour
Atlas_Id 5129
Phylum Soft Tissues::Inflammatory myofibroblastic tumor

Clinics and Pathology

Disease Inflammatory myofibroblastic tumors
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

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(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

    Genes involved and Proteins

    Gene Name TPM3
    Location 1q25
    Protein 284 amino acids, 33 kDa; coiled coil structure; role in Calcium dependant actin-myosin interaction

    Gene Name ALK
    Location 2p23
    Protein 1620 amino acids; 177 kDa; glycoprotein (200 kDa mature protein) ; membrane associated tyrosine kinase receptor

    Result of the chromosomal anomaly

    Hybrid Gene
    Description 5' TPM3 - 3' ALK
    Fusion Protein
    Description 104 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
      

    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
     
    Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.
    Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ
    Cancer research. 1999 ; 59 (12) : 2776-2780.
    PMID 10383129
     
    Aberrant ALK tyrosine kinase signaling. Different cellular lineages, common oncogenic mechanisms.
    Ladanyi M
    The American journal of pathology. 2000 ; 157 (2) : 341-345.
    PMID 10934137
     
    A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation.
    Lamant L, Dastugue N, Pulford K, Delsol G, Mariamé B
    Blood. 1999 ; 93 (9) : 3088-3095.
    PMID 10216106
     
    TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.
    Lawrence B, Perez-Atayde A, Hibbard MK, Rubin BP, Dal Cin P, Pinkus JL, Pinkus GS, Xiao S, Yi ES, Fletcher CD, Fletcher JA
    The American journal of pathology. 2000 ; 157 (2) : 377-384.
    PMID 10934142
     
    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
     
    Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma.
    Siebert R, Gesk S, Harder L, Steinemann D, Grote W, Schlegelberger B, Tiemann M, Wlodarska I, Schemmel V
    Blood. 1999 ; 94 (10) : 3614-3617.
    PMID 10610119
     
    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(1;2)(q25;p23)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):279-280.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/t0102ID5129.html

    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes ALK

    Translocations implicated (Data extracted from papers in the Atlas)

     t(1;2)(q21;p23) TPM3/ALK

    External links

    Mitelman database t(1;2)(q21;p23) TPM3/ALK [Case List]    t(1;2)(q21;p23) TPM3/ALK [Association List] Mitelman database (CGAP - NCBI)
    arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
     
    Mitelman databaseTPM3/ALK[MCList]    TPM3 (1q21.3) ALK (2p23.2)   t(1;2)(q21;p23)
    TICdbTPM3/ALK    TPM3 (1q21.3) ALK (2p23.2)
     
    Disease databaseSoft Tissues: Inflammatory myofibroblastic tumor with t(1;2)(q21;p23) TPM3/ALK
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed


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