Altered methylation of multiple genes in carcinogenesis of the prostate

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Abstract
The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylation‐specific PCR (MSP): the pi‐class glutathione S‐transferase (GSTP1), retinoic acid receptor beta 2(RARβ2), androgen receptor (AR), death‐associated protein kinase (DAPK), tissue inhibitor of metalloproteinase‐3 (TIMP‐3), O6‐methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer‐1 (HIC‐1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RARβ2, 36% for DAPK, 15% for AR, 6% for TIMP‐3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP‐3, 3% for GSTP1, and 0 for RARβ2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RARβ2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC‐1 methylation. Regarding accumulation of methylated cancer‐related genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RARβ2 genes was noted in PCa. Our findings suggest that methylation of cancer‐related genes may be involved in carcinogenesis of the prostate.