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High frequency of alterations in DNA methylation in adenocarcinoma of the prostate
Author(s) -
Santourlidis Simon,
Florl Andrea,
Ackermann Rolf,
Wirtz HansChristian,
Schulz Wolfgang A.
Publication year - 1999
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19990515)39:3<166::aid-pros4>3.0.co;2-j
Subject(s) - dna methylation , methylation , prostate , carcinoma , biology , adenocarcinoma , cancer research , cancer , microbiology and biotechnology , pathology , dna , gene , medicine , gene expression , genetics
BACKGROUND Alterations of DNA methylation have been reported in many human cancers. In prostatic carcinoma, hypermethylation of the GST P gene promoter and an overall decrease in methylcytosine content have been reported. The aim of the present study was to investigate the frequency and extent of these alterations in relation to tumor stage and grade, in order to explore their clinical relevance and to determine their relationship to each other. METHODS DNA from 32 histologically verified adenocarcinomas of the prostate was analyzed for GST P hypermethylation by a semiquantitative PCR method and for overall DNA methylation by quantitative Southern blot analysis or LM‐PCR of LINE‐1 repetitive sequence methylation. RESULTS GST P hypermethylation was detected in 24/32 (75%) specimens, and LINE‐1 hypomethylation in 17/32 (53%). Both alterations tended to increase in frequency and extent with tumor stage. All but 1 of 8 carcinomas with lymph node involvement were positive for GST P hypermethylation. Six of these as compared to 2 out of 24 showed strong hypomethylation ( P = 0.005). Hypermethylation and hypomethylation did not show a quantitative correlation, but all except two samples with weak LINE‐1 hypomethylation also displayed GST P hypermethylation. CONCLUSIONS GST P hypermethylation is an extremely frequent change in prostatic carcinoma which most probably precedes genome‐wide hypomethylation. It appears useful for sensitive detection of prostatic carcinoma, whereas pronounced LINE‐1 hypomethylation may be associated with progressive tumors. Prostate 39:166–174, 1999. © 1999 Wiley‐Liss, Inc.