BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma.

摘要: Malignant mesothelioma (MM) arises from mesothelial cells that line the pleural, peritoneal and pericardial surfaces. The majority of MMs are pleural have been associated with asbestos exposure. Previously, genetically characterized by loss BAP1 (40-60%) as well NF2 (75%) CDKN2A (60%). rare form MM occurs in ~10% cases. With only ~300 cases diagnosed US per year, its link to exposure is not clear mutational landscape unknown. We analyzed somatic 12 epitheloid subtype using copy number analysis (N = 9), whole exome sequencing (N = 7) targeted (N = 12). Peritoneal display few alterations, most samples having less than 10 Mbp total changes, mostly through deletions no high amplification. Chromosome band 3p21 encoding recurrently deleted region (5/9), while, contrast MM, affected. further identified 87 non-silent mutations across 7 sequenced tumors, a median 8 mutated genes tumor, resulting very low mutation rate (median 1.3 10−6). was gene (N = 3/7). In one additional case, entire chromosome 3 leaves non-functional carrying nonsense germline variant, thus suggesting potential genetic predisposition this patient. Finally, cases, we conclude frequently altered losses (N = 3/12), (N = 3/12) or both (N = 2/12) sometimes at sub-clonal level. Our findings suggest major role for susceptibility oncogenesis indicate important molecular differences strategies therapy prevention.