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

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.