Abstract 388: Epigenome-wide profiling identified significant differences in DNA methylation between African-American and European-American men with prostate cancer

Abstract

Abstract Background: DNA methylation is a dynamic epigenetic mark that is essential for mammalian organismal development. For human prostate cancer (PCa), abundant evidence has accumulated to suggest that somatic epigenetic alterations may appear early during cancer development, as well as more commonly and consistently, than genetic changes. Several cancer-associated genes have been reported to show significant differences in DNA methylation pattern in prostate tissues from African-American (AA) and European-American men, but the genome-wide pattern and extent of these differences are largely unknown. The current study investigated genome-wide DNA methylation differences in AA and EA prostate tissue samples with the aim of assessing the variation of genome-wide patterns of DNA methylation. Methods: To comprehensively examine the DNA methylation pattern in AA and EA samples, we used illumina 450 K methylation platform (Infunium Chip) to conduct genome-wide large scale analysis of DNA methylation changes in 7 normal and 3 PCa tissue samples from AA versus 8 normal and 3 PCa tissue samples from EA. This chip interrogates >485,000 CpG methylation sites per sample at single-nucleotide resolution and assigns each site an average beta value for quantitative methylation level. Results: Pathway analysis of the genes with altered methylation patterns identified top canonical pathways for the involvement of cancer related network for genes involved in axonal guidance, antigen presentation, androgen signaling and protein ubiquitination pathways in prostate cancer tissues compared with normal prostate tissues obtained from AA men. On the other hand, the top canonical pathways identified in prostate cancer tissues compared with normal prostate tissues obtained from EA men are genes involved in epithelial-mesenchymal transition, p53 signaling, nucleotide sugars metabolism and germ cell-sertoli cell junction signaling pathways. Conclusion: Using this quantitative sequencing-based approach, our work uncovers significant global DNA methylation alterations in AA versus EA prostate tissues and provides a mechanistic explanation for the disease disparity. Citation Format: Bernard Kwabi-Addo, Songping Wang, Joseph Devaney. Epigenome-wide profiling identified significant differences in DNA methylation between African-American and European-American men with prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 388. doi:10.1158/1538-7445.AM2014-388