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• W3109175066 abstract "990 Epigenetic alteration such as promoter hypermethylation of gene, as well as genetic abnormality such as gene mutation, occurs frequently during the pathogenesis of human cancers. Recent studies exhibit the increasing observations that both epigenetic and genetic changes combine to determine the phenotype of cancer. Aberrant Wnt signaling is an early progression event in 90% of colorectal cancers (CRC) and occurs through mutations mainly of APC and less often of β-catenin. Recently, it has been reported that promoter methylation of Wnt-antagonist genes, such as SFRPs, Dkks and Wif-1, contributes to the initiation and progression of CRC. In this study, we aimed to clarify whether DNA promoter methylation of SFRP1 and Dkk1 may be used as parameters for predicting prognosis in CRC, and whether K-Ras mutation, which is commonly observed in CRC, has any association with these methylations. In addition, we analyzed the influence of the combination of SFRP1 and Dkk1 methylation and K-Ras mutation on prognosis in CRC. Tissue samples from 118 CRC patients who underwent surgical resection were examined. The methylation status of SFRP1 and Dkk1 and the sequences of exon 1 of K-Ras were determined by methylation specific PCR and direct sequencing, respectively, using genomic DNA extracted from paraffin-embedded blocks. Correlation between these factors and clinicopathologic findings/patients survival were examined. As a result, DNA methylations of SFRP1 and Dkk1 were detected in 75 of 118 (63.6%) tumors and in 26 (22.0%), respectively. K-Ras mutations were identified in 40 of 118 (33.9%). There was a significant correlation between K-Ras mutation and SFRP1 (77.5%; 31 of 40; p=0.03) but not Dkk1 (30.0%; 12 of 40; p=0.13). SFRP1 and Dkk1 methylation showed no associations with overall survival and other clinicopathological findings in CRC patients. In CRC without K-Ras mutation, however, patients with at least one or two methylated genes had poorer overall survival compared with no methylated genes (p=0.035). To contrary, in the cases of K-Ras mutation, patients with the methylation of either or both genes tended to have better survival than patients with no methylation (p=0.052). Classifying CRC based on SFRP1 and Dkk1 methylation status and K-Ras mutation may be a clinically powerful predictor of patient outcome." @default.
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• W3109175066 date "2008-05-01" @default.
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• W3109175066 title "Influence of methylation of the Wnt-antagonist SFRP1 and Dkk1 on outcome in colorectal cancer is reversed by K-Ras mutation" @default.
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