title: Genetic characterization of Chinese hereditary non-polyposis colorectal cancer by DHPLC and multiplex PCR.
abstract: BACKGROUND
  Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease due to germline mutations of human mismatch repair genes, mainly hMLH1 and hMSH2. The aim of the present study was to identify the point mutations and large genomic deletions of hMLH1 and hMSH2 genes in 14 Chinese HNPCC families.
  
  
  METHODS
  Fourteen families fulfilling the Chinese HNPCC criteria were involved in this study. Genomic DNA isolated from peripheral blood samples was analyzed. Point mutations were detected by denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing. Multiplex polymerase chain reaction and GeneScan analysis were employed to detect the large genomic deletions of these two genes.
  
  
  RESULTS
  Four of the 14 probands (29%) had sequence abnormalities that probably affect the protein function in the exonic regions of hMLH1 and hMSH2 genes. Included were one complete deletion of exons 1-7 and one missense mutation of the hMSH2 gene, and one nonsense mutation and one missense mutation of the hMLH1 gene. The large genomic deletion accounted for 25% (one out of four) of all mutations. Half (two out of four, 50%) of the mutations were missense mutation. In addition, one silent mutation, four polymorphisms in the exonic regions and four polymorphisms in the intronic regions were also discovered.
  
  
  CONCLUSIONS
  Point mutations and large genomic deletions of the hMLH1 and hMSH2 genes were responsible for nearly one-third of Chinese HNPCC families. Detection of large genomic deletions should be involved in the routine screening manual for HNPCC families.
authors.affiliation: Cancer Research Institute, 2nd Hospital, Zhejiang University School of Medicine, 88 Jie-Fang Road, Hangzhou, 310009 PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Huang
authors.forename: Shan-rong
authors.initials: SR
authors.lastname: Cai
authors.forename: Yong-mao
authors.initials: YM
authors.lastname: Song
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Su-zhan
authors.initials: SZ
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D044466:Asian People / Q000235:genetics; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein