E. Feng1,2, J. M. A. Vo-Phamhi1,3, A. Foye2,4, J. Vinson5, J. C. Hong1, S. J. Freedland6,7, J. Alumkal8, H. Beltran9, C. Morrissey10, P. Nelson11, A. Chinnaiyan12, C. Sawyers13, R. Aggarwal2,4, E. Small2,4, D. Quigley2, M. Sjostrom2, S. G. Zhao14, and W. S. Chen1,2; 1Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 2Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 3Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 4Department of Medicine, University of California San Francisco, San Francisco, CA, 5Prostate Cancer Clinical Trials Consortium, New York, NY, 6Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, 7Durham VA Medical Center, Durham, NC, 8University of Michigan, Ann Arbor, MI, 9Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Womens Hospital, Boston, MA, 10Department of Urology, University of Washington School of Medicine, Seattle, WA, 11Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, 12Departments of Pathology and Urology, University of Michigan, Ann Arbor, MI, 13Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 14Department of Human Oncology, University of Wisconsin-Madison, Madison, WI
Purpose/Objective(s): 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. Materials/
Methods: Genomic and clinicopathologic data from five 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 481 men with mCRPC, tumors from African American patients demonstrated higher expression of MYC pathway genes (FDR q=0.03) and lower expression of IFN-?, IL-6/JAK/STAT3, and inflammatory pathway genes (FDR q<0.001) compared to tumors from white patients. TMPRSS2:ERG gene fusions were observed more frequently in tumors from white 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. Conclusion: Racial differences in expression of prostate cancer driver gene pathways (including potential clinically actionable pathways of IFN-? and JAK/STAT) and DNA alterations (including TMPRSS2:ERG gene fusion) were observed. Our findings highlight the importance racial diversity in future genomic profiling and clinical trials efforts.
