Racial variation in the advanced prostate cancer genome.

Background: Racial differences in metastatic castration-resistant prostate cancer (mCRPC) genomes have not yet been fully studied. We aimed to investigate transcriptomic, mutational, and clinical differences by race in a large multi-institutional cohort of men with mCRPC.

Methods: Genomic and clinicopathologic data from four mCRPC tumor biopsy cohorts were obtained and aggregated. Gene set enrichment analyses were performed to assess pathway-level differences in gene expression by patient race. DNA alteration frequencies of known prostate cancer driver genes and clinical outcomes were compared across racial groups.

Results: In our cohort of 445 men with mCRPC, tumors from African American patients (N = 26) demonstrated higher expression of MYC pathway genes (FDR q = 0.03) and lower expression of IFN-γ, IL-6/JAK/STAT3, and inflammatory pathway genes (FDR q < 0.001) compared to tumors from European American patients. TMPRSS2:ERG gene fusions were observed more frequently in tumors from European American compared to African American patients (41% vs. 11%, P = 0.015). Asian patients (N = 9) and other racial groups comprised a small minority of our cohort. No differences in overall survival were noted across racial groups.

Conclusions: Despite demonstrating similar clinical outcomes, cancers from African Americans display distinct tumor biology. Specifically, we observed racial differences in expression of prostate cancer driver gene pathways (including potential clinically actionable pathways of IFN-γ and JAK/STAT) and DNA alterations, including TMPRSS2:ERG gene fusion. Our findings highlight the importance of racial diversity in future genomic profiling and clinical trials efforts.