title: Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer.
abstract: OBJECTIVE
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, General Hospital of Beijing Military Command, Dongcheng District, Beijing, China. jianqiu@263.net
authors.forename: Jian-Qiu
authors.initials: JQ
authors.lastname: Sheng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Ji
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
authors.forename: Hong
authors.initials: H
authors.lastname: Mu
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Ji-Sheng
authors.initials: JS
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.forename: Zi-Qin
authors.initials: ZQ
authors.lastname: Sun
authors.forename: Zi-Tao
authors.initials: ZT
authors.lastname: Wu
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Xia
authors.forename: Shi-Rong
authors.initials: SR
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D018095:Germ-Line Mutation; D006801:Humans; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D004247:DNA; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein