Correlation of tumor BRAF mutations and MLH1 methylation with germline MMR gene mutation status: a literature review assessing utility of tumor features for MMR variant classification

Lynch Syndrome is a heritable disorder characterized by increased risk of colorectal, endometrial and other cancers. It is caused by mutations in the DNA mismatch repair (MMR) genes. We conducted a literature review of published studies that investigated MMR gene mutation status and two tumor characteristics commonly used to exclude individuals with colorectal cancer from MMR gene mutation testing: BRAF V600E mutation status and MLH1 promoter methylation status. We showed that BRAF mutation status and MLH1 methylation are strong negative predictors of MMR mutation status, but are not definitive. These tumor characteristics should be used in conjunction with other data points in statistical models that predict likely mutation status. (By Dr Amanda B Spurdle, http://jmg.bmj.com/content/49/3/151)