title: Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer.
abstract: OBJECTIVE
  The present study was designed to determine the frequency of germline mutations in the hMLH1 and hMSH2 genes in 31 families suspected of having hereditary nonpolyposis colorectal cancer who do not fulfill the criteria of the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer but in whom a genetic basis for colon cancer is strongly suspected and 45 patients with sporadic early-onset colorectal cancer who developed colorectal cancer before the age of 40 years without any family history of colorectal cancer.
  
  
  METHODS
  Genomic DNAs were prepared from peripheral blood samples of patients who were tested. All coding exons and exon-intron borders of these two genes were screened, first with the polymerase chain reaction-single-strand conformation polymorphism method, followed by sequencing of the DNA fragments displaying an abnormal single-strand conformation polymorphism pattern.
  
  
  RESULTS
  In 31 families with suspected hereditary nonpolyposis colorectal cancer, we found six different germline mutations in seven unrelated families, including one missense mutation and three frame-shift mutations in the hMLH1 gene and one missense mutation and one frame-shift mutation in the hMSH2 gene. Totally, frequency of mutation was 23 percent, 16 percent and 7 percent in the hMLH1 and hMSH2, respectively. Only one missense mutation of the hMSH2 gene was identified in 45 patients (2 percent) with sporadic early-onset colorectal cancer. The mutation detection rate in families with suspected hereditary nonpolyposis colorectal cancer was significantly higher than that of patients with sporadic early-onset colorectal cancer (P < 0.05).
  
  
  CONCLUSIONS
  Our definition of suspected hereditary nonpolyposis colorectal cancer is useful in the diagnosis of hereditary nonpolyposis colorectal cancer and for identifying those families who need genetic presymptomatic diagnosis. Our results indicate that it may be important to perform DNA testing in families suspected of having hereditary nonpolyposis colorectal cancer. On the other hand, we only detected a low mutation rate (2 percent) in 45 patients with sporadic early-onset colorectal cancer.
authors.affiliation: Laboratory of Cell Biology, Cancer Research Center, Seoul National University College of Medicine, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Yuan
authors.forename: H J
authors.initials: HJ
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: J G
authors.initials: JG
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013223:Statistics as Topic
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