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  • Title: Infrequent somatic Fas mutations but no evidence of Bcl10 mutations or t(11;18) in primary cutaneous MALT-type lymphoma.
    Author: Grønbaek K, Ralfkiaer E, Kalla J, Skovgaard GL, Guldberg P.
    Journal: J Pathol; 2003 Sep; 201(1):134-40. PubMed ID: 12950026.
    Abstract:
    Genetic alterations that allow tumour cells to evade apoptosis have recently been identified as key features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT-type lymphoma). The t(11;18), which produces the putative anti-apoptotic fusion protein API2-MALT1, has been identified in a large proportion of extracutaneous MALT-type lymphomas and a smaller fraction of tumours harbour mutations that inactivate the pro-apoptotic functions of Fas and Bcl10. The present study has examined the status of these genes in 19 primary cutaneous B-cell lymphomas (PCBCLs), 12 of which were MALT-type lymphomas according to the WHO classification. None of the 19 PCBCLs carried the t(11;18) and tumour-specific Bcl10 alterations were not identified at the genomic level or at the mRNA level. Somatic Fas mutations causing truncation of the Fas receptor were identified in two MALT-type lymphomas. Both patients with Fas mutant PCBCL exhibited benign conditions of dysregulated lymphoproliferation. One had autoimmune diabetes and rheumatoid arthritis and the other had a 25-year history of recurrent cutaneous pseudo-lymphomas. It is suggested that Fas mutation permits the survival and hence the accumulation of autoreactive B cells. This expansion of autoreactive B cells is analogous to the expansion of B cells chronically stimulated by exogenous antigens in the development of MALT-type lymphoma.
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