title: The analysis for identifying large DNA fragment aberrations of MSH2 and MLH1 genes from familial colorectal cancer in China.
abstract: OBJECTIVE
  To investigate the frequency of large fragment aberrations of MSH2 and MLH1 genes from Chinese colorectal cancer (CRC) patients with family history.
  
  
  METHODS
  Sixteen exons of MSH2, nineteen exons of MLH1 and seven DNA sequences from the other genes of the samples were screened and checked by multiplex ligation dependent probe amplification (MLPA). First, the methodology was confirmed by testing the positive and negative control samples. Then, 32 CRC or hereditary nonpolyposis colorectal cancer (HNPCC) patients with family history and 20 cases of sporadic CRC were applied to investigate for the large fragment aberrations of MSH2 and MLH1 genes.
  
  
  RESULTS
  The genomic DNA fragment deletions of all positive controls were identified and verified by MLPA. Three cases of 32 familial (hereditary) CRC/HNPCC were detected and identified to be the germline heterozygous deletions of MSH2 gene, of which exons 1-7 were deleted from patient No.3, exon 11 from No.25 and exons 2-6 from No.11. However, no genomic DNA fragment aberration of either MSH2 or MLH1 gene was uncovered from 20 sporadic CRC.
  
  
  CONCLUSIONS
  Large DNA fragment aberrations of MSH2 gene was a frequent cause of Chinese HNPCC and CRC patients with family history, and the identification of those aberrations should be included in the regular genetic analysis for CRC/HNPCC patients.
authors.affiliation: Department of Molecular Biology, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Xiao-rong
authors.initials: XR
authors.lastname: Liu
authors.forename: Yan-qin
authors.initials: YQ
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jin-tian
authors.initials: JT
authors.lastname: Li
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Yuan-ying
authors.initials: YY
authors.lastname: Zhang
authors.forename: Ya-ping
authors.initials: YP
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D020137:Base Pair Mismatch; D002681:China; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein