title: Infrequent somatic Fas mutations but no evidence of Bcl10 mutations or t(11;18) in primary cutaneous MALT-type lymphoma.
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.
authors.affiliation: Institute of Cancer Biology, The Danish Cancer Society, Copenhagen, Denmark. kjg@cancer.dk
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbaek
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiaer
authors.forename: Jörg
authors.initials: J
authors.lastname: Kalla
authors.forename: Gunhild L
authors.initials: GL
authors.lastname: Skovgaard
authors.forename: Per
authors.initials: P
authors.lastname: Guldberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002352:Carrier Proteins / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic; D019014:fas Receptor / Q000235:genetics*
chemical_list: C415943:API2-MALT1 fusion protein, human; D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D019014:fas Receptor