t(2;22)(p23;q11) MYH9/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 (ALCL): 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;22)(p23;q11) 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;22) case was that of a 12 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
    MYH9 (myosin, heavy polypeptide 9, non-muscle)
    Location
    22q12.3
    Protein description
    codes for the non-muscle myosin II, heavy chain type A. Non-muscle myosin II is involved in motility and cell division
    Germinal mutations
    in patients with May-Hegglin anomaly and Fechner syndrome
    Somatic mutations
    MYH9/ALK fusion protein in ALCL (see above)

    Result of the Chromosomal Anomaly

    Description

    5 MYH9 - 3 ALK2201 amino acids, 220 kDa. N term MYH9 fused to the 556 C-term amino acids from ALK (i.e. the entire cytoplasmic portion of ALK with the tyrosine kinase domain), instead of the classic 562 C-term amino acids from ALK seen in other ALK fusion proteins

    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
    128001562003Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma.29
    195452842009Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular-histological correlation.21

    Bibliography

    Pubmed IDLast YearTitleAuthors
    109949992000Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.Drexler HG et al
    128001562003Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma.Lamant L 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

    Citation

    Jean-Loup Huret

    t(2;22)(p23;q11) MYH9/ALK

    Atlas Genet Cytogenet Oncol Haematol. 2003-08-01

    Online version: http://atlasgeneticsoncology.org/haematological/1291/t(2;22)(p23;q11)