Somatic Mutation of BAP1 Can Lead to Expression Loss in Non-Small Cell Lung Carcinoma: Next Generation Sequencing and IHC Analysis in A Large Single Institute Cohort.

As a tumor suppressor, germline and somatic inactivation of BRCA1 associated protein 1 gene () is a common finding in mesothelioma, melanocytic tumors, clear cell renal cell carcinoma and several other epithelial, mesenchymal and neural tumors. Incidence of genetic alterations and subsequent expression loss has not been well established in non-small cell lung carcinoma (NSCLC) by large-scale studies. After IRB approval, a total of 356 NSCLC cases of our institution between July 2016 and June 2020 were reviewed. The study cohort consisted of 214 (60%) adenocarcinomas, 89 (25%) squamous cell carcinomas, and 53 (15%) diagnosed as "non-small cell lung carcinoma" without specified subtype. All tumors underwent comprehensive target cancer gene next generation sequencing (Oncomine Assay). The protein expression status of was subsequently evaluated by immunohistochemistry. somatic mutations were detected in 8 NSCLC tumors (incidence: 2.2%). Tumors harboring mutations were all diagnosed at advanced stage and carried at least one additional genetic alteration. Immunohistochemically, four tumors showed complete loss of BAP1 protein expression, including two adenocarcinomas which harbored different missense mutations and another two with bioinformatically predicated deleterious frameshifting mutations. Compared with known loss associated other malignancies, such as mesothelioma, inactivation of by somatic mutation is a rare occurrence in NSCLC. mutations and loss of expression in NSCLC are accompanied by other complex genetic alternations, suggesting mutation maybe a late event NSCLC carcinogenesis.