Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer

AIM:To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS:A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation detection. RESULTS:High frequency microsatellite instability occurred in 25 probands (83.3%) of HNPCC family.Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability.Pathogenic muta-tion occurred in 14 samples and 3 novel mutational sites were discovered.Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1.Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands.The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%.The rate of the two methods in combination with methylation detection was 63.3%.CONCLUSION: Scientific and rational detection strategy can improve the detection rate of HNPCC.Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC.