Promoter methylation status and expression of TMS1 gene in human epithelial ovarian cancer

Gene silencing associated with aberrant DNA methylation of promoter CpG islands is one mechanism through which tumor suppressor genes are inactivated in human cancers. TMS1 (target of methylation-induced silencing) is a CpG island-associated gene that functions in the regulation of apoptosis. In this study, we examined the DNA methylation status of the TMS1 promoter in ovarian cancer cell lines and tissues by methylation-specific PCR (MSP) and its mRNA expression by reverse transcription and quantitative PCR. Aberrant methylation of TMS1 was present in 7/12 ovarian cancer cell lines and 8/20 primary ovarian cancer tissues. The median value of relative TMS1 gene expression in cancers with methylation (0.15) was significantly lower than that in cancers without methylation (13.9) (P<0.001). The expression of the TMS1 gene was relatively high (48.5) in the normal ovarian cDNA library. TMS1 gene expression was restored by treatment with the demethylating agent 5-aza-2'-deoxycitidine in the OV90 cell line, which lacks the TMS1 transcript. Our results suggest that aberrant methylation of TMS1 may play a role in the pathogenesis of ovarian cancer.