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  • Title: Silencing of secreted frizzled-related protein genes in MSI colorectal carcinogenesis.
    Author: Tanaka J, Watanabe T, Kanazawa T, Tada T, Kazama Y, Tanaka T, Nagawa H.
    Journal: Hepatogastroenterology; 2008; 55(85):1265-8. PubMed ID: 18795670.
    Abstract:
    BACKGROUND/AIMS: The epigenetic pathway of colorectal carcinogenesis has recently become the focus of attention. The most common epigenetic change is the promoter hypermethylation of tumor suppressor genes. Secreted frizzled-related proteins have been identified and are reported to act as inhibitors of the Wnt signaling pathway. It has also been reported that microsatellite unstable cancers show more frequent hypermethylation in tumor suppressor genes and less frequent APC mutation. METHODOLOGY: Fifty-one sporadic colorectal cancers were investigated, of which 22 were MSI-H and 29 were MSI-L/MSS. Methylation-specific polymerase chain reaction was performed to detect the methylation status of SFRP1, 2 and 5 genes. RESULTS: All of the samples showed hypermethylation in the promoter region of SFRP1. MSI-H cancers showed more frequent hypermethylation in SFRP2 than MSI-L/MSS cancers, though there was no statistical significance. SFRP5 promoter hypermethylation was significantly more frequent in MSI-H cancers than in MSI-L/MSS cancers. CONCLUSIONS: SFRPs may act as an important inhibitor of the Wnt signaling pathway in MSI-H cancers.
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