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Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer.

Point mutations of KRAS and BRAF genes are thought to be important in carcinogenesis of colon cancer. In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer. However, a consensus has not been established regarding the correlation between point mutations of KRAS or BRAF and carcinogenesis in patients with endometrial cancer, which is closely related to colon cancer. Therefore, we analyzed aberrant hypermethylation of the hMLH1 gene, microsatellite instability (MSI), and point mutations of KRAS and BRAF in 44 samples of sporadic endo-metrial cancer, with the aim of examining the mechanism of carcinogenesis in patients with endometrial cancer. Aberrant hMLH1 hypermethylation was found in 17 of the 44 cases (38.6%) and showed a significant positive correlation with MSI (p=0.02). This suggests that an abnormal MMR mechanism plays an important role in carcinogenesis of sporadic endometrial cancer. Point mutation of KRAS was found in 6 of the 44 cases (13.6%), but no BRAF V600E mutation was detected. These data suggest that the BRAF V600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer. This is supported by the relatively few previous reports indicating a correlation between endometrial cancer and the BRAF V600E mutation. Identification of new candidates for the target gene for abnormal MMR in endometrial cancer requires further work.