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Hypermethylation of CpG island loci and hypomethylation of LINE-1 and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features

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Authors
Cho, N-Y; Kim, B-H; Choi, M; Yoo, E J; Moon, K C; Cho, Y-M; Kim, D; Kang, G H
Issue Date
2006-11-30
Publisher
John Wiley & Sons
Citation
J Pathol 2007;211(3):269-277
Keywords
Adenocarcinoma/genetics/*metabolismAlu Elements/genetics*CpG IslandsDNA/analysis*Gene Expression Regulation, Neoplastic*DNA MethylationLong Interspersed Nucleotide Elements/geneticsNeoplasm StagingPolymerase Chain Reaction/methodsPrognosis*Promoter Regions, GeneticProstatic Hyperplasia/genetics/metabolismProstatic Neoplasms/genetics/*metabolismRepetitive Sequences, Nucleic Acid
Abstract
Promoter CpG island hypermethylation is an important carcinogenic event in prostate adenocarcinoma. Regardless of tissue type, human cancers have in common both focal CpG island hypermethylation and global genomic hypomethylation. The present study evaluated CpG island loci hypermethylation and LINE-1 and Alu repeat hypomethylation in prostate adenocarcinoma, analysed the relationship between them, and correlated these findings with clinicopathological features. We examined 179 cases of prostate adenocarcinoma and 30 cases of benign prostate hypertrophy for the methylation status of 22 CpG island loci and the methylation levels of LINE-1 and Alu repeats using methylation-specific polymerase chain reaction and combined bisulphite restriction analysis, respectively. The following 16 CpG island loci were found to display cancer-related hypermethylation: RASSF1A, GSTP1, RARB, TNFRSF10C, APC, BCL2, MDR1, ASC, TIG1, RBP1, COX2, THBS1, TNFRSF10D, CD44, p16, and RUNX3. Except for the last four CpG island loci, hypermethylation of each of the remaining 12 CpG island loci displayed a close association with one or more of the prognostic parameters (ie preoperative serum prostate specific antigen level, Gleason score sum, and clinical stage). Prostate adenocarcinoma with hypermethylation of each of ASC, COX2, RARB, TNFRSF10C, MDR1, TIG1, RBP1, NEUROG1, RASSF1A, and GSTP1 showed a significantly lower methylation level of Alu or LINE-1 than prostate adenocarcinoma without hypermethylation. In addition, hypomethylation of Alu or LINE-1 was closely associated with one or more of the above prognostic parameters. These data suggest that in tumour progression a close relationship exists between CpG island hypermethylation and the hypomethylation of repetitive elements, and that CpG island hypermethylation and DNA hypomethylation contribute to cancer progression.
ISSN
0022-3417 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17139617

http://hdl.handle.net/10371/10048
DOI
https://doi.org/10.1002/path.2106
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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