Abstract 1011: Transposable element patterns across genetic ancestries in prostate cancer patients

Abstract Introduction: Prostate cancer (PCa) is a significant burden to American men with African ancestry (AA). The mechanism of how ancestry contributes to aggressive PCa in AA patients is not well understood. We have identified a difference between races in endogenous retroviruses (ERVs) expression. In prostate and cervical cancer, we have demonstrated that ERV expression signatures are useful for identifying patients at the greatest risk of disease progression. There is consistency in mortality rates for black men in the US, Caribbean, and Sub-Saharan Africa suggesting that shared ancestry is a common risk factor. Using ERVcaller we investigated polymorphic transposon elements (TE) and ERV insertions unique to tumor cells compared to normal blood in prostate cancer patients of African (AF) and European ancestry (EU). Method: ERVcaller software detects retrotransposons including Alu, LINE1, SVA, and HERV-K types using whole genome sequencing (WGS). We gathered publicly available WGS data (FASTQ files) from the European Nucleotide Archive (SRA accession SRP119289). These were derived from paired blood and tumor samples from 6 AF and 9 EU PCa patients. We processed this data with ERVcaller, revealing TE insertions present in each patient sample (i.e., blood or tumor). We identified tumor-exclusive and blood-exclusive insertions by excluding overlapping TE insertions between tumor and blood samples. These insertions were then analyzed for differences using a T-test in R Studio. Results: Statistical analysis revealed significant differences in the number of TE insertions in the tumors of AF patients (mean = 50.00) compared to their EU (mean = 31.89) counterparts (p-value < 0.0038). In addition, we found no significant differences in TE insertions in blood samples of AF patients (mean = 35.50) relative to EU patients (mean = 32.78; p-value > 0.56), suggesting that this differential insertion pattern is isolated to the affected tumor region. Conclusion: ERVs have previously demonstrated important roles in the development of various diseases. Our findings demonstrate significant variations in TE insertions in tumors of PCa patients across genetic ancestries. Citation Format: Nicholas Korvink, Lucas Ueta, Hannah Park, Vinay Kumar, Farah Rahmatpanah. Transposable element patterns across genetic ancestries in prostate cancer patients [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 1011.