The molecular heterogeneity and clinical impact of genomic driver alterations in prostate cancer.

Recurrent genomic driver alterations are identified in 97% of primary prostate tumors, revealing four distinct oncotypes with varying clinical outcomes.

• Why it matters: Understanding the molecular heterogeneity of prostate cancer is crucial for improving diagnosis, prognosis, and targeted therapies, addressing gaps in knowledge about driver mutations and mechanisms of dysregulation.
• What they did: Using whole genome sequencing of 961 primary prostate tumors from 1001 men, the study quantifies recurrent mutations, structural variants, and copy number alterations, identifying key driver genes and mechanisms, including regulatory element disruptions.
• The result: The findings uncover the full spectrum of genomic alterations, stratify tumors into oncotypes with different metastasis-free survival, and highlight genome-informed therapeutic targets, advancing biomarker and treatment development.