title: Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer.
abstract: OBJECTIVE
  Germline mutations in four DNA mismatch repair genes are known to cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC). The rapidly increasing information about these mutations needs to be collected and appropriately stored to facilitate further studies on the biological and clinical significance of the findings.
  
  
  METHODS
  The International Collaborative Group on HNPCC has established a database of DNA mismatch repair gene mutations and polymorphisms. In this report, 126 predisposing mutations were analyzed.
  
  
  RESULTS
  A majority of the mutations affected either the Mut L homologue (MLH) 1 (n = 75) or the Mut S homologue (MSH) 2 (n = 48) and were quite evenly distributed, with some clustering in MSH2 exon 12 and MLH1 exon 16. Most MSH2 mutations consisted of frameshift (60%) or nonsense changes (23%), whereas MLH1 was mainly affected by frameshift (40%) or missense alterations (31%). Although most mutations were unique, a few common recurring mutations were identified. Of the families studied (n = 202), 82% met the Amsterdam criteria and 15% did not; the general mutation profile was similar in both groups.
  
  
  CONCLUSIONS
  The construction of mutation profiles will facilitate the development of diagnostic strategies in HNPCC.
authors.affiliation: Department of Medical Genetics, Haartman Institute, Helsinki, Finland. Paivi.Peltomaki@helsinki.fi
authors.forename: P
authors.initials: P
authors.lastname: Peltomäki
authors.forename: H F
authors.initials: HF
authors.lastname: Vasen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D004198:Disease Susceptibility; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D007438:Introns; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes