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BAP1, a tumor suppressor gene driving malignant mesothelioma #MMPMID28713672
Cheung M; Testa JR
Transl Lung Cancer Res 2017[Jun]; 6 (3): 270-8 PMID28713672show ga
Like cancer generally, malignant mesothelioma (MM) is a genetic disease at the cellular level. DNA copy number analysis of mesothelioma specimens has revealed a number of recurrent sites of chromosomal loss, including 3p21.1, 9p21.3, and 22q12.2. The key inactivated driver genes located at 9p21.1 and 22q12.2 were discovered two decades ago as being the tumor suppressor loci CDKN2A and NF2, respectively. Only relatively recently was the BAP1 gene determined to be the driver gene at 3p21.1 that is somatically inactivated. In 2011, we reported germline mutations in BAP1 in two families with a high incidence of mesothelioma and other cancers such as uveal melanoma (UM). As a result of a flurry of research activity over the last 5?6 years, the BAP1 gene is now firmly linked causally to a novel tumor predisposition syndrome (TPDS) characterized by increased susceptibility to mesothelioma, UM, cutaneous melanoma (CM) and benign melanocytic tumors, as well as several other cancer types. Moreover, results from recent in vivo studies with genetically engineered Bap1-mutant mouse models and new functional studies have provided intriguing biological insights regarding BAP1?s role in tumorigenesis. These and other recent findings offer new possibilities for novel preventative and therapeutic strategies for MM patients.
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Transl+Lung+Cancer+Res 2017 ; 6 (3): 270-8
