Abstract A112: Integrative epigenomic and transcriptomic analyses of kidney cancers from African Americans and European Americans

Abstract

Abstract Background: Kidney cancer ranks as a top ten leading site of new cancer cases (~64,000) in the United States each year. Renal cell carcinoma (RCC) is the most common type of kidney cancer (90% cases), with clear cell RCC (ccRCC) being the most prevalent histology (70% RCC cases). RCC risk factors include nonmodifiable, modifiable, environmental, and occupational causes. RCC subtypes each have a different histology, clinical course, and response to therapy, in addition to distinctive genetic and molecular alterations. African Americans (AA) have higher incidence rates of ccRCC than European Americans (EA) for reasons that are unclear. Biologic determinants of this cancer health disparity have been largely understudied. Recent work has identified population-specific genomic drivers in ccRCC tumors from AA compared with EA. To date, no study has explored epigenomic or transcriptomic determinants of kidney cancer health disparities in AA. Hypothesis: We hypothesized population-specific changes in DNA methylation, between AA and EA, drive differences in ccRCC biology through regulation of the transcriptome. Methods: Comparative integrative genomic and transcriptomic analyses were performed using clinical demographic and ccRCC data (Illumina 450K methylation array and mRNA-seq) from TCGA (n=50 AA, 266 EA) and Partek Genomics Suite. Results: Differential methylation analysis discovered 2,048 genes varied significantly by race (P value + FDR = ≤0.01). Gene Ontology Enrichment Score (ES) analysis revealed these genes were involved with various molecular functions (nucleic acid binding ES 38.52, protein binding ES 38.03), biologic processes (cellular metabolic process ES 78.60), and cellular component localization (intracellular organelles ES 87.24). Differential gene expression analysis revealed 3,296 genes were altered in AA compared with EA race (P value + FDR = ≤0.01). GSEA analysis revealed distinct biologic pathways were enriched. Conclusion and Future Directions: Collectively, our data suggest that DNA methylation and mRNA expression drive differences in tumor biology amongst AA and EA kidney cancer patients. Future studies include integrating miRNA expression data, validating these findings in a separate cohort, profiling other RCC histologies for population-specific signatures, and using kidney cancer cell lines from AA and EA to explore novel biologic mechanisms for therapeutic purposes. Citation Format: Heinric Williams, Khadijah A. Mitchell. Integrative epigenomic and transcriptomic analyses of kidney cancers from African Americans and European Americans [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A112.