Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry. Clinical follow-up revealed increased biochemical recurrence (BCR) among Black patients compared to White patients with high-grade PCa. Transcriptomic analysis identified differential alternative RNA splicing events (ARSs) between Black and White PCa patients. Genes undergoing genetic ancestry-concordant ARSs in high-grade or low-grade tumors involved cancer promoting genes. Most genes undergoing genetic ancestry-concordant ARSs did not exhibit differential aggregate gene expression or alternative polyadenylation. A number of the genetic ancestry-concordant ARSs associated with BCR; thus, genetic ancestry-concordant RNA splice variants may represent unique targets for PCa precision oncology.
NPJ precision oncology. 2025 Jan 29*** epublish ***
Muthana Al Abo, Wen-Chi Foo, Lauren E Howard, Shannon McGue, Bonnie Lacroix, Julie Kephart, Angela Clayton, Blair Thornburg, Monika Anand, Michael B Rothberg, Shannon J McCall, Jiaoti Huang, Thomas A Esther, Judd W Moul, Michael N Ferrandino, Thomas J Polascik, Cary N Robertson, Brant A Inman, Andrew J Armstrong, Yuan Wu, Terry Hyslop, Daniel J George, Steven R Patierno, Jennifer A Freedman
Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of Medicine, Durham, NC, 27710, USA., Department of Internal Medicine, Duke University School of Medicine, Durham, NC, 27710, USA., Flatiron Health, New York, NY, 10013, USA., Tempus Compass, Chicago, IL, 60654, USA., Colorado Urology, Denver, CO, 80111, USA., Division of Urology, Department of Oncology, Lawson Health Research Institute, Western University, London, ON, Canada., Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA., Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of Medicine, Durham, NC, 27710, USA. .