Germline mutations in the BRCA1-associated protein (BAP1) gene (MIM # 603089) are associated with a substantially increased risk for developing melanoma, mesothelioma, and renal cell carcinoma. Somatic inactivation of the BAP1 gene was noted in these and other tumors types, including esophageal cancer and cholangiocarcinoma. The favorable response of BRCA1/2-associated tumors to poly (ADP-ribose) polymerase (PARP) inhibitor therapy, raises the possibility that tumors harboring BAP1 mutations may exhibit similar sensitivity to PARP inhibitor therapy. Given the possibility that BAP1 alterations may have therapeutic implications, this study was aimed to describe the spectrum of tumors that harbor BAP1 alterations. The Foundation Medicine database was queried for known or likely pathogenic BAP1 genomic variants through July 2019. Overall, 4982/374,694 (1.81%) tumors harbored pathogenic BAP1 genomic alterations. Highest rates were noted in mesothelioma (45.24%), cholangiocarcinoma (13.37%), renal cell carcinoma (10.52%), thymic cancer (8.16%), salivary gland cancer (6.18%), and melanoma (5.1%). There were 59 unique BAP1 short variants detected in at least 10 samples. More same tissue tumors of squamous cell histology harbored BAP1 alterations than adenocarcinomas. The current study highlights tumor types that display higher than previously appreciated rates of somatic BAP1 genomic alterations.

BRCA1相关蛋白 ( BAP1)基因 (MIM # 603089) 中的种系突变与患黑色素瘤、间皮瘤和肾细胞癌的风险显着增加有关。在这些和其他肿瘤类型中注意到BAP1基因的体细胞失活，包括食道癌和胆管癌。BRCA1/2相关肿瘤对聚（ADP-核糖）聚合酶（PARP）抑制剂治疗的有利反应，增加了携带BAP1突变的肿瘤可能表现出与 PARP 抑制剂治疗相似的敏感性的可能性。鉴于BAP1的可能性改变可能具有治疗意义，本研究旨在描述携带BAP1改变的肿瘤谱。到 2019 年 7 月，对 Foundation Medicine 数据库进行了查询，了解已知或可能的致病性BAP1基因组变异。总体而言，4982/374,694 (1.81%) 个肿瘤具有致病性BAP1基因组改变。间皮瘤 (45.24%)、胆管癌 (13.37%)、肾细胞癌 (10.52%)、胸腺癌 (8.16%)、唾液腺癌 (6.18%) 和黑色素瘤 (5.1%) 的发病率最高。在至少 10 个样本中检测到59 个独特的BAP1短变体。更多相同组织的鳞状细胞组织肿瘤含有BAP1改变不如腺癌。当前的研究强调了显示出高于先前认可的体细胞BAP1基因组改变率的肿瘤类型。