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

• Published in: The Journal of pathology Vol. 211; no. 3; pp. 269 - 277
• Main Authors: Cho, N-Y, Kim, B-H, Choi, M, Yoo, EJ, Moon, KC, Cho, Y-M, Kim, D, Kang, GH
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.2007; Wiley
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adult; Aged; Alu Elements - genetics; Biological and medical sciences; CpG island; CpG Islands; DNA - analysis; DNA Methylation; Gene Expression Regulation, Neoplastic; Humans; hypomethylation; Investigative techniques, diagnostic techniques (general aspects); Long Interspersed Nucleotide Elements - genetics; Male; Medical sciences; Middle Aged; Neoplasm Staging; Nephrology. Urinary tract diseases; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase Chain Reaction - methods; Prognosis; Promoter Regions, Genetic; prostate adenocarcinoma; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - metabolism; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Repetitive Sequences, Nucleic Acid; Tumors of the urinary system; Urinary tract. Prostate gland; Urinary system disease; Prostate disease; Nucleotide sequence; Malignant tumor; CpG island; prostate adenocarcinoma; Anatomic pathology; Alu sequence; GC rich sequence; DNA; hypomethylation; DNA methylation; Methylation; Male genital diseases; Prostate cancer
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2106

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. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.