Distinct mutations in MLH1 and MSH2 genes in Hereditary Non-polyposis Colorectal Cancer (HNPCC) families from China

  • Wei, Wenqian (Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University) ;
  • Liu, Fangqi (Colorectal Surgery, Shanghai Cancer Hospital of Fudan University) ;
  • Liu, Lei (Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University) ;
  • Li, Zuofeng (Shanghai Center for Bioinformation Technology) ;
  • Zhang, Xiaoyan (School of Life Science and Technology, Tongji University) ;
  • Jiang, Fan (Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University) ;
  • Shi, Qu (Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University) ;
  • Zhou, Xiaoyan (Colorectal Surgery, Shanghai Cancer Hospital of Fudan University) ;
  • Sheng, Weiqi (Colorectal Surgery, Shanghai Cancer Hospital of Fudan University) ;
  • Cai, Sanjun (Colorectal Surgery, Shanghai Cancer Hospital of Fudan University) ;
  • Li, Xuan (Shanghai Center for Bioinformation Technology) ;
  • Xu, Ye (Colorectal Surgery, Shanghai Cancer Hospital of Fudan University) ;
  • Nan, Peng (Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University)
  • Received : 2011.01.04
  • Accepted : 2011.02.22
  • Published : 2011.05.31


Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed.




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