Unexpected Germline Mutations In A Pan-Cancer Analysis Including Sarcoma, Renal, And Other Cancers

1584Background: Multi-gene testing for cancer predisposition is increasingly utilized in clinical care. Although the diagnostic yield and management implications of such testing in breast, ovarian and colorectal cancer are relatively well understood, data for other cancer types are still emerging. In this study we retrospectively examined 39,147 patients referred for hereditary cancer syndrome testing for pathogenic germline variants in 80 cancer risk genes, focusing on those patients with renal, sarcoma, paraganglioma, melanoma, and pancreatic cancers. Methods: Test results and personal/family history were extracted from a sequential series of de-identified clinical test reports. Data for genes not clinically ordered were analyzed under an IRB approved research protocol. Common low penetrance risk alleles were excluded. Results: Overall, 14.3% (5,589) of patients carried germline pathogenic mutations in 80 cancer risk genes. Of the 949 patients with renal cancer 20% (190) were positive, and 44% of these ...