Mutational and splicing landscape in a cohort of 43,000 patients tested for hereditary cancer
Carolyn Horton, Ashley Cass, Blair R. Conner, Lily Hoang, Heather Zimmermann, Nelly Abualkheir, David Burks, Dajun Qian, Bhuvan Molparia, Huy Gia Vuong, Holly LaDuca, Jessica Grzybowski, Kate Durda, Robert Pilarski, Jessica Profato, Katherine M Clayback, Martin C. Mahoney, Courtney Schroeder, Wilfredo Torres‐Martinez, Aaron Elliott, Elizabeth Chao, Rachid Karam
Abstract
DNA germline genetic testing can identify individuals with cancer susceptibility. However, DNA sequencing alone is limited in its detection and classification of mRNA splicing variants, particularly those located far from coding sequences. Here we address the limitations of splicing variant identification and interpretation by pairing DNA and RNA sequencing and describe the mutational and splicing landscape in a clinical cohort of 43,524 individuals undergoing genetic testing for hereditary cancer predisposition.