Aberrant methylation of the HACE1 gene is frequently detected in advanced colorectal cancer.

Abstract

BACKGROUND: It has been recently reported that HACE1, the E3 ubiquitin ligase, is epigenetically inactivated in human Wilms' tumors and HACE1 expression was also down-regulated in colon carcinomas. MATERIALS AND METHODS: The methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 32 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the HACE1 gene was detected in 9 out of the 32 (28%) primary colon carcinomas, suggesting that the aberrant methylation of HACE1 was frequently observed in colorectal cancer. The clinicopathological data were then correlated with these results. A significant increase was observed in the maximal tumor size of the methylated HACE1 tumors (p = 0.0304). Moreover, a trend was shown towards preferentially developing lymph node metastasis in the methylated HACE1 carcinomas (p = 0.0612). CONCLUSION: HACE1 might act as a tumor suppressor in colorectal carcinomas and HACE1 methylation might present a malignant potential in colorectal cancer.