Approximately 25% of the tumors had alterations in the PI3K or MAPK signaling pathways, with frequent loss of PTEN (17%), or activation of PIK3CA, PIK3CB, AKT1, and MTOR. In addition to identifying the major subtypes among primary prostate cancers, results from this study revealed substantial molecular heterogeneity and underscored potentially actionable molecular defects. This evidence concerns the gene PIK3CA and Familial prostate cancer.