Inherited Predisposition to Malignant Mesothelioma (MM) Due to Mutations in DNA Repair Genes.

8504Background: Identifying the profile of DNA repair genes predisposing to MM will enable treatment options for patients (pts) and risk assessment for their families. Methods: In this prospective study of the natural history of MM (NCT01950572) we enrolled 239 consecutive pts independent of site of disease, family history of cancer, age at diagnosis, ethnicity, or asbestos exposure. Germline DNA was sequenced for all 239 pts, identifying mutations of all classes in 73 DNA repair genes. Tumor DNA from 12 pts with germline BAP1 mutations was evaluated by whole exome sequencing. Results: Of the 239 pts, 29 (12%) carried a pathogenic germline mutation in a DNA repair gene: BAP1 (N = 17 pts), CHEK2 (N = 5), PALB2 (N = 2), and BRCA2, MLH1, POT1, TP53, and MRE11A (N = 1 each). Pts with mutations were more likely to be female (P = 0.02) and to have been diagnosed with another cancer (P = 0.009). Pts with germline mutations were more likely to have a 1o relative with a diagnosis of MM (P < 0.0001), melanoma (P = ...