Coordinate hypermethylation at specific genes in prostate carcinoma precedes LINE-1 hypomethylation

Abstract

In prostate carcinoma (PCa) increased DNA methylation (‘hypermethylation’) occurs at specific genes such as GSTP1. Nevertheless, overall methylation can be decreased (‘hypomethylation’) because methylation of repetitive sequences like LINE-1 retrotransposons is diminished. We analysed DNA from 113 PCa and 36 noncancerous prostate tissues for LINE-1 hypomethylation by a sensitive Southern technique and for hypermethylation at eight loci by methylation-specific PCR. Hypermethylation frequencies for GSTP1, RARB2, RASSF1A, and APC in carcinoma tissues were each >70%, strongly correlating with each other (P−6). Hypermethylation at each locus was significantly different between tumour and normal tissues (10⁻¹¹<P82% of PCas. PCa may fall into three classes, that is, with few DNA methylation changes, with frequent hypermethylation, or with additional LINE-1 hypomethylation.