Aiming to unveil a significant part of the genetic background behind hereditary/familial prostate cancer, we will explore our whole-exome sequencing data from 45 prostate cancer families (39 duos and six trios), focusing on recurrently mutated genes. For mutations found in at least two families, and considering the history of founder mutations in our population, we will start by investigating possible founder effects by constructing and analyzing haplotypes. To elucidate the contribution of genes with different mutations to inherited prostate cancer predisposition, full sequencing will be performed in the remaining 417 cases, either by targeted sequencing or, as a long term approach, by whole-exome sequencing, which is also expected to reveal additional candidate genes. To validate the role of the most promising genes in carcinogenesis, tumors from variant carriers will be characterized, and the mechanisms by which specific mutations promote carcinogenesis will be evaluated using in vitro and/or in vivo models.