Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm
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Altered DNA methylation in cancer cells is characterized by focal CpG island hypermethylation and diffuse genomic hypomethylation. Both types of aberrant methylation are frequently found in human prostate adenocarcinoma (PCa). Prostatic intraepithelial neoplasm (PIN), a precursor lesion of PCa, has been demonstrated to contain CpG island hypermethylation, but little is known about the role of DNA hypomethylation. We analyzed the methylation status at 12 CpG island loci and at two repetitive DNA elements (LINE-1 and SAT2) from normal prostate (n = 20), PIN (n = 25), and PCa (n = 35) tissues using MethyLight assay or combined bisulfite restriction analysis. The methylation levels in LINE-1 and SAT2 decreased with progression of lesion types from normal prostate to PIN to PCa (P < 0.05), whereas promoter CpG island loci displayed increased methylation. Ten genes were found to be hypermethylated in a cancer-specific manner and were further analyzed in another set of PCa tissues (n = 64). The number of methylated genes was closely associated with TNM stage, Gleason sum, and preoperative serum PSA levels (P = 0.020, 0.073, 0.033, respectively). These results suggest that genomic hypomethylation and CpG island hypermethylation, common among PCas, are early events in prostate carcinogenesis and may be implicated in the development of PIN.
KeywordsCpG island DNA methylation Prostate adenocarcinoma Prostate intraepithelial neoplasm
This study was supported by the 21C Frontier Functional Human Genome Project from the Ministry of Science & Technology in Korea (FG06-11-02 to G.H.K.) by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0720540) and by the second stage Brain Korea 21 project.
Conflict of interest
The authors declare that they have no conflict of interest.
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