Glutathione S-transferases (GSTs) are a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents. The π-class GST has been associated with preneoplastic and neoplastic changes. Recently, it has been reported that regulatory sequences near the GSTP1 gene, which encodes the human π-class GST, 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. GSTP1 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 GSTP1 was associated with loss of expression demonstrated by immunohistochemistry. Our results suggest that aberrant methylation of GSTP1 may contribute to the carcinogenetic process in breast and renal carcinomas.

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M. E. is a recipient of a Spanish Ministerio de Educacion y Cultura Award, J. G. H. is a Valvano Foundation Scholar, S. B. B. and J. G. H. receive research funding and are entitled to sales royalties from ONCOR, which is developing products related to research described in this paper. The terms of this arrangement have been reviewed and approved by The Johns Hopkins University in accordance with its conflict of interest policies.

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