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Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm

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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.

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Acknowledgments

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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Authors and Affiliations

  1. Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Nam-Yun Cho & Gyeong Hoon Kang

  2. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea

    Jung Ho Kim, Kyung Chul Moon & Gyeong Hoon Kang

Authors
  1. Nam-Yun Cho
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  2. Jung Ho Kim
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  3. Kyung Chul Moon
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Correspondence to Gyeong Hoon Kang.

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Supplementary figure

Comparison of the methylation levels of ten genes in three groups of prostatic carcinomas, which were arbitrarily defined by their Gleason scores: tumors with a score ≤3 + 3, tumors with a score of 3 + 4 or 4 + 3, and tumors with a score ≥4 + 4. The examined genes were sorted ordered from highest to lowest P values from left to right along the x axis. Error bar indicates SEM. (DOC 20 KB)

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Cho, NY., Kim, J.H., Moon, K.C. et al. Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm. Virchows Arch 454, 17–23 (2009). https://doi.org/10.1007/s00428-008-0706-6

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  • DOI: https://doi.org/10.1007/s00428-008-0706-6

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