Abstract 4955: Somatic mutation frequency in prostate cancer patients of different ancestries and age of onset

Abstract Background: Prostate cancer (PCa) varies significantly in outcomes based on age of onset and genetic ancestry. Early-onset PCa (EoPCa), diagnosed in men under 55, exhibits aggressive behavior, poor differentiation, and resistance to hormonal therapies, resulting in worse outcomes compared to late-onset PCa (LoPCa). African American (AA) men face more aggressive disease and higher incidence rates than White men with European heritage (EA), even after accounting for socioeconomic factors. Investigating somatic mutations in PCa is essential to understanding disease progression, as the biology of EoPCa remains poorly defined. Comparing mutational frequencies in AA and EA men with EoPCa and LoPCa provides key insights into these disparities and informs targeted interventions. Methods: We analyzed the mutational status of EoPCa and LoPCa in AA and EA patients. We isolated DNA in tumor tissue from FFPE prostatectomy tissues using Qiagen’s FFPE DNA Purification Plus Kit. DNA samples from three patients in each cohort (AA LoPCa, AA EoPCa, EA LoPCa, EA EoPCa) were investigated for 81 somatic mutations across 13 genes using real-time PCR. Mutational analysis was performed with Qiagen’s qBiomarker Prostate Cancer Gene Panel, an assay designed to detect PCa specific sequence alterations. DNA and qBiomarker Probe Master Mix were prepared following the manufacturer’s protocol. Relative fold gene expression was calculated using the 2-∆∆Ct (delta-delta Ct) method, with DNA from normal epithelial prostate tissue serving as the control. Values exceeding a threshold of 4 were considered indicative of mutations. Results: The analysis of somatic mutation frequencies, with their position and substitution, revealed notable differences across race and the combined factors of race and age of onset. Our analysis revealed higher mutation rates in AA patients for CTNNB1 98 C>T (83.3% AA vs. 66.7% in EA) and KRAS 34 G>A (66.7% AA vs. 33.3% in EA), mutations not previously reported as elevated in AA PCa. When examining race and age of onset together, distinct patterns emerged. Among LoPCa patients, the TP53 827 C>T mutation was found in 100% of AA patients compared to 66.7% of EA patients, while the HRAS 35 G>T mutation was present in 33.3% of AA patients but absent in EA patients. In EoPCa, AA patients exhibited higher frequencies of the CTNNB1 101 G>T mutation (33.3% AA vs. 0% in EA) and KRAS 35 G>C mutation (33.3% AA vs. 0% in EA). Conclusion: These mutations, previously unexamined in the context of race and age of onset, highlight disparities in the mutational landscape of PCa. Citation Format: Tara S. Jennings, Anton N. Nguyen, Weiping Chu, Dan Mercola, Farah Rahmatpanah. Somatic mutation frequency in prostate cancer patients of different ancestries and age of onset [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4955.