Integrative analysis of genomic driver alterations in prostate cancer

Prostate cancer is a common malignancy with a heterogeneous disease course. Prior studies have identified a paucity of point mutations in protein-coding genes, and only a few clinically relevant driver alterations. The multinational Pan Prostate Cancer Group, using the whole genome sequencing dataset from 1001 men, performed an integrative analysis of cancer driver genes by quantifying recurrent genomic alterations among small mutations, structural variants, and copy number alterations in 961 primary prostate tumor samples. The authors identified at least one recurrent somatic or germline alteration in 97% of tumors and identified putative driver genes and mechanisms of dysregulation including frequently altered regulatory elements. One quarter of tumors have acquired genome-informed therapeutic targets. Unsupervised analysis of alterations reveals four oncotypes with distinct genetic and clinical characteristics, including two clinically unfavorable oncotypes with shorter metastasis-free survival. The authors conclude that this study uncovers the spectrum and recurrence patterns of genomic driver alterations in primary prostate cancers.