Aberrant methylation of the netrin-1 receptor genes UNC5C and DCC detected in advanced colorectal cancer.
BACKGROUND
UNC5C and DCC, the netrin-1 receptors, belong to the functional dependence receptors family, which shares the ability to induce apoptosis in the absence of their ligands. Recently, two reports indicated that UNC5C and DCC methylation was closely associated with loss of gene expression in colorectal cancer. These results prompted us to examine the methylation status of the UNC5C and DCC genes in the colorectal carcinomas we surgically removed.


METHODS
The methylation status of the UNC5C and DCC genes were examined in primary carcinomas and the corresponding normal tissues derived from 50 patients with colorectal cancer using quantitative methylation-specific polymerase chain reaction (qMSP). The correlation between the methylation status and the clinicopathologic findings was then evaluated.


RESULTS
Aberrant methylation of the netrin-1 receptor genes were detected in 41 of the 50 (82%) primary colon cancers, suggesting that the aberrant methylation of netrin-1 receptors was frequently observed in colorectal cancer. The clinicopathologic data were then correlated with this result.


CONCLUSIONS
A significant difference was observed in the Dukes stage (p = 0.0438). Netrin-1 receptors might act as a tumor suppressor in colorectal cancers, and thus 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
Mizukami
Hiroki
H
Shirahata
Atsushi
A
Goto
Tetsuhiro
T
Sakata
Makiko
M
Sanada
Yutaka
Y
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D016163:Genes, DCC / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009414:Nerve Growth Factors / Q000235:genetics; D000075386:Netrin Receptors; D000075388:Netrin-1; D011956:Receptors, Cell Surface / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C115727:UNC5C protein, human; D000075388:Netrin-1