High frequency of alterations in DNA methylation in adenocarcinoma of the prostate.
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.
Santourlidis
S
S
Urologische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany.
Florl
A
A
Ackermann
R
R
Wirtz
H C
HC
Schulz
W A
WA
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000368:Aged; D015139:Blotting, Southern; D019175:DNA Methylation; D005819:Genetic Markers; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*
D005819:Genetic Markers; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase