CYTIDINE METHYLATION OF REGULATORY SEQUENCES NEAR THE PI-CLASS GLUTATHIONE-S-TRANSFERASE GENE ACCOMPANIES HUMAN PROSTATIC CARCINOGENESIS

Hypermethylation of regulatory sequences at the locus of the pi-class glutathione S-transferase gene GSTP1 was detected in 20 of 20 human pr ostatic carcinoma tissue specimens studied but not in normal tissues o r prostatic tissues exhibiting benign hyperplasia. In addition, a stri king decrease in GSTP1 expression was found to accompany human prostat ic carcinogenesis. Immunohistochemical staining with anti-GSTP1 antibo dies failed to detect the enzyme in 88 of 91 prostatic carcinomas anal yzed. In vitro, GSTP1 expression was limited to human prostatic cancer cell lines containing GSTP1 alleles with hypomethylated promoter sequ ences; a human prostatic cancer cell line containing only hypermethyla ted GSTP1 promoter sequences did not express GSTP1 mRNA off polypeptid es. Methylation of cytidine nucleotides in GSTP1 regulatory sequences constitutes the most common genomic alteration yet described for human prostate cancer.