关键词：基因工程；基因；甲基化；前列腺癌
摘 要：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.