Makiko Sakata

Aberrant Methylation of the Netrin-1 Receptor Genes UNC5C and DCC Detected in Advanced Colorectal Cancer

BackgroundUNC5C 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.MethodsThe 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.ResultsAberrant 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.ConclusionsA 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.

Methylation of the WNT5A gene is frequently detected in early gastric carcinoma.

BACKGROUND/AIMS Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown. METHODOLOGY Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric 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 WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209). CONCLUSIONS WNT5A was more frequently methylated in early gastric carcinomas.