Abstract
Identifying inherited cancer predisposition genes remains challenging. We leveraged the skin's high UV-mutagenic burden to discover susceptibility genes by studying patients with high frequency of basal cell carcinomas (hfBCC). We found that hfBCC patients had three-fold higher internal malignancy prevalence and identified a novel candidate EPHB2 cancer susceptibility mutation associated with BCC and prostate cancer. These findings demonstrate the skin's potential as a powerful platform for discovering cancer predisposition variants.