The diverse genomic landscape of low−risk prostate cancer.

74Background: Among men with clinically low-risk prostate cancer, we have previously documented heterogeneity in terms of clinical characteristics and genomic risk scores. In this study, we aimed to study the underlying tumor biology of this patient population, by interrogating patterns of gene expression among men with clinically low-risk tumors. Methods: Prostate biopsies from 427 patients considered potentially suitable for active surveillance underwent central pathology review and genome-wide expression profiling. These cases were compared to 1290 higher-risk biopsy cases with diverse clinical features from a prospective genomic registry. Average genomic risk (AGR) was determined from 18 published prognostic signatures, and MSigDB Hallmark gene sets were analyzed using bootstrapped clustering methods. These sets were examined in relation to clinical variables and pathologic and biochemical outcomes using multivariable regression analysis. Results: 408 (96%) of biopsies passed RNA quality control. Base...