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©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 28, 2009; 15(8): 983-989
Published online Feb 28, 2009. doi: 10.3748/wjg.15.983
Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer
Jian-Qiu Sheng, Hong Zhang, Min Ji, Lei Fu, Hong Mu, Ming-Zhi Zhang, Ji-Sheng Huang, Min Han, Ai-Qin Li, Zhi Wei, Zi-Qin Sun, Zi-Tao Wu, Chang-Hong Xia, Shi-Rong Li
Jian-Qiu Sheng, Hong Zhang, Min Ji, Lei Fu, Ai-Qin Li, Zhi Wei, Zi-Tao Wu, Chang-Hong Xia, Shi-Rong Li, Department of Gastroenterology, General Hospital of Beijing Military Command, Beijing 100700, China
Hong Mu, Department of Gastroenterology, Chinese PLA 253 Hospital, Hohhot 010051, Inner Mongolian Autonomous Region, China
Ming-Zhi Zhang, Department of Oncology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
Ji-Sheng Huang, Min Han, Shangqiu People’s Hospital, Shangqiu 476000, Henan Province, China
Zi-Qin Sun, Department of Gastroenterology, General Hospital of Jinan Military Command, Jinan 250034, Shandong Province, China
Author contributions: Sheng JQ and Li SR designed the research; Sheng JQ, Zhang H, Ji M, Fu L, Li AQ, Wei Z, Wu ZT, and Xia CH performed the research; Li AQ, Mu H, Zhang MZ, Huang JS, Han M and Sun ZQ collected the biological samples; Sheng JQ and Fu L analyzed the data; Sheng JQ, Fu L and Li SR wrote the paper.
Correspondence to: Jian-Qiu Sheng, Department of Gastroenterology, General Hospital of Beijing Military Command, Nanmencang 5, Dongcheng district, Beijing 100700, China. jianqiu@263.net
Telephone: +86-10-66721014
Fax: +86-10-66721299
Received: October 10, 2008
Revised: January 20, 2009
Accepted: January 27, 2009
Published online: February 28, 2009
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 mutation 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.
