Promoter and histone methylation and p16INK4A gene expression in colon cancer

The inactivation of the cyclin-dependent kinase inhibitor p16INK4A gene by hypermethylation is observed in numerous types of cancer. New findings indicate that DNA and histone methylation act in concert in gene silencing. In this study, we investigated the methylation status of the p16INK4A gene promoter and the histone 3 lysine 9 residue in the tumors and matched normal tissue samples from patients with colorectal cancer and analyzed their association with gene expression. The methylation and expression of the p16INK4A gene were analyzed by real-time PCR, and histone methylation was analyzed by chromatin immunoprecipitation followed by real-time PCR. p16INK4A expression was significantly higher in the tumors compared to normal tissue. Mono-, di- and trimethylation levels of the H3K9 residue were similar in the tumor and normal tissue samples. We did not observe any significant correlation between p16INK4A methylation or expression and clinical parameters. Our results suggest that epigenetic modifications of the p16INK4A gene and histone lysine methylation do not play a major role in colon carcinogenesis.