t(2;17)(p23;q23) CLTC/ALK

2003-08-01   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.
  • 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;17)(p23;q23) has so far been described in only 1 case, 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.
  • 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. The t(2;17) case was that of a 14 yrs old girl.

    Genes Involved and Proteins

    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
    Gene name
    CLTC (clathrin heavy polypeptide)
    Location
    17q23.1
    Protein description
    1675 amino acids, 191 kDa; component of the vesicles matrix originated from the plasma membrane or the golgi

    Result of the Chromosomal Anomaly

    Description

    5 CLTC - 3 ALKthe 1634 N term amino acids from CLTC fused to the 562 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain)

    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
    127639272003ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases.55
    127501592003ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma.46
    152086562004Differential effects of X-ALK fusion proteins on proliferation, transformation, and invasion properties of NIH3T3 cells.45
    211349802011Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma.27
    214946212011Inhibition of anaplastic lymphoma kinase (ALK) activity provides a therapeutic approach for CLTC-ALK-positive human diffuse large B cell lymphomas.18
    129202292003ALK+, CD30-, CD20- large B-cell lymphoma containing anaplastic lymphoma kinase (ALK) fused to clathrin heavy chain gene (CLTC).18
    154929982004ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement.12
    235883722013STAT3 pathway is activated in ALK-positive large B-cell lymphoma carrying SQSTM1-ALK rearrangement and provides a possible therapeutic target.10
    224744492012Anaplastic lymphoma kinase-positive large B-cell lymphoma: an underrecognized aggressive lymphoma.9
    218552322011ALK-positive extramedullary plasmacytoma with expression of the CLTC-ALK fusion transcript.9
    158524312006ALK-positive diffuse large B-cell lymphoma.9
    241427402014CLTC-ALK fusion as a primary event in congenital blastic plasmacytoid dendritic cell neoplasm.7
    245838372014ALK-positive inflammatory myofibroblastic tumor of the abdomen with widespread microscopic multifocality.6
    195212802009ALK-positive diffuse large B-cell lymphoma with the t(2;17)(p23;q23).6
    159210122005ALK-positive diffuse large B-cell lymphoma: two more cases and a brief literature review.6
    347271722022ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.5
    196363982009Anaplastic lymphoma kinase-positive large B-cell lymphoma: a distinct clinicopathological entity.5
    184585032008[Cytomorphology and molecular characterization of CLTC-ALK rearrangement in 2 cases of ALK-positive diffuse large B-cell lymphoma with extensive bone marrow involvement].5
    340198662021Identification of novel ALK fusions using DNA/RNA sequencing in immunohistochemistry / RT-PCR discordant NSCLC patients.2
    324203022020Central nervous system relapse in a pediatric anaplastic large cell lymphoma patient with CLTC/ALK translocation treated with alectinib: A case report.1
    351175832020Exome sequencing identified six copy number variations as a prediction model for recurrence of primary prostate cancers with distinctive prognosis.1
    127873122003Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype.1
    351645782022Pediatric Non-Myofibroblastic Primitive Spindle Cell Tumors with ALK Gene Rearrangements and Response to Crizotinib.0
    341417902021Diagnosis and treatment of pediatric anaplastic lymphoma kinase-positive large B-cell lymphoma: A case report.0
    331543172020Anaplastic Lymphoma Kinase positive large B cell lymphoma of ileocaecal mesentery: A case report.0

    Bibliography

    Pubmed IDLast YearTitleAuthors
    121125242002Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.Cools J et al
    109949992000Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.Drexler HG et al
    113803912001Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Morris SW et al
    110900482000CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.Stein H et al

    Summary

    Fusion gene

    CLTC/ALK CLTC (17q23.1) ALK (2p23.2) M|CLTC/ALK CLTC (17q23.1) ALK (2p23.2) M t(2;17)(p23;q23)|CLTC/ALK CLTC (17q23.1) ALK (2p23.2) TIC

    Citation

    Jean-Loup Huret

    t(2;17)(p23;q23) CLTC/ALK

    Atlas Genet Cytogenet Oncol Haematol. 2003-08-01

    Online version: http://atlasgeneticsoncology.org/haematological/1290/t(2;17)(p23;q23)

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