TY - JOUR T1 - Discovery and reporting of clinically-relevant germline variants in advanced cancer patients assessed using whole-exome sequencing JF - bioRxiv DO - 10.1101/112672 SP - 112672 AU - Tuo Zhang AU - Alessandro Romanel AU - Kenneth W. Eng AU - Hanna Rennert AU - Adrian Y. Tan AU - Yaohua Xue AU - Joanna Cyrta AU - Juan Miguel Mosquera AU - Andrea Sboner AU - Ivan Iossifov AU - Steven M. Lipkin AU - Jenny Xiang AU - Xiaojun Feng AU - Peter Nelson AU - Himisha Beltran AU - Colin C. Pritchard AU - Mark A. Rubin AU - Francesca Demichelis AU - Olivier Elemento Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/01/112672.abstract N2 - Purpose In precision cancer care, WES-based analysis of tumor-normal samples helps reveal somatic alterations but can also identify cancer-associated germline variants important for disease surveillance, treatment choice and cancer prevention. WES can also identify germline secondary findings impacting risk of cardiac, neurodegenerative or metabolic diseases. In patients with advanced cancer, the frequency of reportable secondary findings encountered with WES is not well defined.Methods To address this question, we analyzed a cohort of 343 patients with advanced, metastatic cancer for whom we have performed tumor and germline WES interrogating more than 21,000 genes using a CLIA/CLEP approved assay.Results 17% of patients in our cohort have one or more reportable germline variants, including patients with pathogenic variants in the BRCA1 and BRCA2 genes. The frequency of non-cancer clinically relevant germline variants (8.8%) was within the range of two control non-cancer cohorts (11.0% and 6.5%). The frequency of variants in cancer-associated genes was significantly higher (p<0.0005) in our advanced cancer cohort (8.2%) compared to control cohorts (2.7% and 3.8%). More than 50% of patients with reportable germline cancer variants had a family history of cancer.Conclusion these results stress the importance of returning germline results found during somatic genomic tumor testing. ER -