Infrequent somatic Fas mutations but no evidence of Bcl10 mutations or t(11;18) in primary cutaneous MALT‐type lymphoma

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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. Copyright © 2003 John Wiley & Sons, Ltd.