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.


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).


CONCLUSIONS
HACE1 might act as a tumor suppressor in colorectal carcinomas and HACE1 methylation might present a malignant potential in colorectal cancer.
Hibi
Kenji
K
Department of Surgery, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama 227-8501, Japan. kenjih-ngy@umin.ac.jp
Sakata
Makiko
M
Sakuraba
Kazuma
K
Shirahata
Atsushi
A
Goto
Tetsuhiro
T
Mizukami
Hiroki
H
Saito
Mitsuo
M
Ishibashi
Kazuyoshi
K
Kigawa
Gaku
G
Nemoto
Hiroshi
H
Sanada
Yutaka
Y
D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
C497506:HACE1 protein, human; D044767:Ubiquitin-Protein Ligases