Genetic similarity between cancers and comorbid Mendelian diseases identifies candidate driver genes.

ABSTRACT: Despite large-scale cancer genomics studies, key somatic mutations driving cancer, and their functional roles, remain elusive. Here, we propose that analysis of comorbidities of Mendelian diseases with cancers provides a novel, systematic way to discover new cancer genes. If germline genetic variation in Mendelian loci predisposes bearers to common cancers, the same loci may harbour cancer-associated somatic variation. Compilations of clinical records spanning over 100 million patients provide an unprecedented opportunity to assess clinical associations between Mendelian diseases and cancers. We systematically compare these comorbidities against recurrent somatic mutations from more than 5,000 patients across many cancers. Using multiple measures of genetic similarity, we show that a Mende

SUBMITTER: Melamed RD 

PROVIDER: S-EPMC4416231 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature