Racial variation in the advanced prostate cancer genome

Emily M Feng; Jenny Vo-Phamhi; Aishwarya N Subramanian; Mikhail Dias; Adam Foye; Jake Vinson; Julian C Hong; Stephen J Freedland; Joshi J Alumkal; Himisha Beltran; Colm Morrissey; Peter S Nelson; Arul M Chinnaiyan; Rahul Aggarwal; Eric J Small; David A Quigley; Martin Sjöström; Shuang G Zhao; William S Chen

doi:10.1038/s41391-025-00949-w

Racial variation in the advanced prostate cancer genome

Prostate Cancer Prostatic Dis. 2025 Mar 31. doi: 10.1038/s41391-025-00949-w. Online ahead of print.

Authors

Emily M Feng^{1

2}, Jenny Vo-Phamhi^{1

3}, Aishwarya N Subramanian^{1

2}, Mikhail Dias^{1

2}, Adam Foye^{1

4}, Jake Vinson⁵, Julian C Hong^{1

2}, Stephen J Freedland^{6

7}, Joshi J Alumkal⁸, Himisha Beltran⁹, Colm Morrissey¹⁰, Peter S Nelson^{11

12

13}, Arul M Chinnaiyan¹⁴, Rahul Aggarwal^{1

4}, Eric J Small^{1

4}, David A Quigley^{1

15

16}, Martin Sjöström^{1

17

18}, Shuang G Zhao^{19

20}, William S Chen^{21

22}

Affiliations

¹ Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
² Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
³ Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
⁴ Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
⁵ Prostate Cancer Clinical Trials Consortium (PCCTC), New York, NY, USA.
⁶ Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷ Section of Urology, Durham VA Medical Center, Durham, NC, USA.
⁸ Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
⁹ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.
¹¹ Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹² Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹³ Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
¹⁴ Departments of Pathology and Urology, University of Michigan, Ann Arbor, MI, USA.
¹⁵ Department of Urology, University of California San Francisco, San Francisco, CA, USA.
¹⁶ Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
¹⁷ Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden.
¹⁸ Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
¹⁹ Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.
²⁰ Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
²¹ Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. will.chen@ucsf.edu.
²² Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. will.chen@ucsf.edu.

PMID: 40164700
DOI: 10.1038/s41391-025-00949-w

Abstract

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.