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Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm

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Authors
Cho, Nam-Yun; Kim, Jung Ho; Moon, Kyung Chul; Kang, Gyeong Hoon
Issue Date
2008-12-02
Publisher
Springer Verlag
Citation
Virchows Arch 454:17-23
Keywords
CpG island; Prostate adenocarcinoma; Prostate intraepithelial neoplasm; DNA methylation
Abstract
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.
ISSN
0945-6317
Language
English
URI
http://hdl.handle.net/10371/4562
DOI
https://doi.org/10.1007/s00428-008-0706-6
https://doi.org/10.1007/s00428-008-0706-6
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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