Inactivation of Glutathione 5-Transferase PI Gene by Promoter Hypermethylation in Human Neoplasia1

Glutathione S-transferases (GST's) are a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents. The ir-class (ÂiSThas been associated with preneoplastic and neoplastic changes. Recently, it has been reported that regulatory se quences near the GSTP1 gene, which encodes the human 7T-classGST, are commonly hypermethylated in prostatic carcinomas. In the present study, we studied more than 300 primary human tumors originating in other organs for aberrant methylation of GSTP1 using methylation-specific PCR. GSTPI hypermethylation was most frequent in breast and renal carcinoma, showing aberrant methylation in 30 and 20% of the cases, respectively. Other tumor types showed promoter methylation only rarely or not at all. Hypermethylation of GSTPI was associated with loss of expression demonstrated by immunohistochemistry. Our results suggest that aberrant methylation of GSTPI may contribute to the carcinogenetic process in breast and renal carcinomas.