BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes.

摘要: Recently, it was shown that the oncogenic activation of BRAF, a member RAS/RAF family kinases, by V600E mutation is characteristic for sporadic colon tumors with microsatellite instability. Further, to associate silencing mismatch repair (MMR) gene MLH1 hypermethylation. Moreover, BRAF mutations proved be absent in from hereditary nonpolyposis colorectal cancer syndrome (HNPCC) families germline MMR genes and MSH2. These data suggest involved only tumorigenesis. In order further support this hypothesis, we have extended analysis different subset HNPCC without BRAF-V600E were analysed automatic sequencing 38 MSH6 also (suspected) do not MLH1, MSH2 MSH6. All patients belong families. No detected 14 no found 23 MMR-negative families, which 13 fulfilled Amsterdam criteria 10 suspected as they positive Bethesda criteria. Overall, our reinforce concept tumorigenesis HNPCC. The detection suggests origin disease absence alterations findings potential impact genetic testing diagnostics use exclusion or molecular marker cancer.