Abstract 983: Characterizing somatic copy number alterations in African American renal cell carcinoma patients

Abstract Background: Renal cell carcinoma (RCC) has one of the highest mortality rates of all urologic cancers in the US. Somatic copy number alteration (SCNA) profiles have been linked with RCCC mortality. African American (AA) RCC patients have higher mortality and lower survival rates when compared to European Americans (EAs) with the disease. AA RCC patients are underrepresented in cancer genomic studies, and RCC mortality and survival disparities may be attributed to SCNA differences. We hypothesize there are distinct population-enriched SCNAs in RCC tumors from AAs compared with EAs. Methods: DNAs were isolated from fresh frozen primary tumors for each RCC patient in the Geisinger-Cooperative Human Tissue Network discovery cohort (n=20), followed by OncoScan CNV (whole-genome copy number microarray) analyses. SCNAs at the genome-wide, chromosomal, chromosomal region, and gene levels were compared in AA (n=10) and EA (n=10) RCC patients using Chromosome Analysis Suite v7. Population differences were calculated using t-tests with Welch’s corrections and multiple unpaired t-tests (P <0.05). STRING was used to identify protein-protein interaction networks and functional enrichment analyses. GraphPad Prism 10 v7 and STRING v12 were used to generate all images. Results: Genome-wide across 22 autosomes, a combined 397 chromosomal regions (n=292 amplifications; 105 deletions) were altered in AA RCC patients compared to 476 chromosomal regions (n=302 amplifications; 174 deletions) in EA RCC patients. We observed AAs had significantly higher amplifications across 13 chromosomes (3, 4, 6, 7, 9, 10, 13-15, 18, 20-22) when compared to their EA counterparts (P <0.05; AA: 164/292, EA: 156/302). A total of 12, 114 genes in AAs and 11, 320 genes in EAs were amplified. Uniquely amplified genes (n=1, 095) in AA RCC patients corresponded with keratin-associated protein (KRTAP) networks (PPI enrichment P value: 3.38e-08). EA RCC patients had 301 uniquely amplified genes that corresponded with trace-amine and natural killer cell lectin-like receptor activities (PPI enrichment P value: 0.000334). Conclusion: KRTAPs are known RCC oncogenes. KRTAP amplifications may drive expression and help to explain more aggressive tumor biology in AA RCC patients. Future Direction: Integrate SCNA data with matched bulk mRNA-sequencing data for each RCC patient. Citation Format: Musinu Zakari, Egbenoma A. Aigboeghian, Khadijah A. Mitchell. Characterizing somatic copy number alterations in African American renal cell carcinoma 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 983.