Global Epigenetic Changes May Underlie Ethnic Differences and Susceptibility to Prostate Cancer
Annual rept. 26 Aug 2012-25 Aug 2013
HOWARD UNIV WASHINGTON DC
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The purpose of the present study is to investigate genome-wide DNA methylation changes in prostate specimens from African-American AA and European-American EA men in order to elucidate the differential DNA methylation changes associated with prostate cancer disparity and identify novel biomarkers for early disease detection. Results We examined the methylation status of a total of 7 normal prostate tissues and 3 prostate cancer tissue samples from AA men and compared it with 8 normal prostate tissues and 3 prostate cancer tissue samples from EA men using the Infunium 450K 484,968 CpG sites that corresponds to 21,221 genes in microarray illumina. Pathway analysis of microarray data for the genes with altered methylation patterns showed the involvement of cancer related genes in networks of axonal guidance, RhoA signaling and androgen signaling in AA specimens versus genes involved in epithelial-mesenchymal transition in EA specimens. Conclusion Our genome-wide methylation analysis suggests differential methylation of several genes in important signaling pathways associated with prostate cancer progression. On-going studies is to validate the illumina microarray results using the methyl-binding domain of MBD2 qMBD-seq technique in order to identify regions that are consistently differentially methylated in AA versus EA specimens. For several genes where antibodies are available we will validate expression in tissue microarray analysis using prostate tissues from AA and EA men who have undergone radical prostatectomy.
- Medicine and Medical Research