title: HNPCC: six new pathogenic mutations.
abstract: BACKGROUND
  Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR). HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in the DNA mismatch-repair genes MLH1, MSH2 and MSH6.
  
  
  METHODS
  Patients with clinical diagnosis of HNPCC were counselled. Tumor specimen were analysed for microsatellite instability and immunohistochemistry for MLH1, MSH2 and MSH6 protein was performed. If one of these proteins was not detectable in the tumor mutation analysis of the corresponding gene was carried out.
  
  
  RESULTS
  We identified 6 frameshift mutations (2 in MLH1, 3 in MSH2, 1 in MSH6) resulting in a premature stop: two mutations in MLH1 (c.2198_2199insAACA [p.N733fsX745], c.2076_2077delTG [p.G693fsX702]), three mutations in MSH2 (c.810_811delGT [p.C271fsX282], c.763_766delAGTGinsTT [p.F255fsX282], c.873_876delGACT [p.L292fsX298]) and one mutation in MSH6 (c.1421_1422dupTG [p.C475fsX480]). All six tumors tested for microsatellite instability showed high levels of microsatellite instability (MSI-H).
  
  
  CONCLUSIONS
  HNPCC in families with MSH6 germline mutations may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations.
authors.affiliation: Human Genetics, University of Bochum, Bochum, Germany. erdmute.kunstmann@rub.de
authors.forename: Erdmute
authors.initials: E
authors.lastname: Kunstmann
authors.forename: Judith
authors.initials: J
authors.lastname: Vieland
authors.forename: Frank E
authors.initials: FE
authors.lastname: Brasch
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Hahn
authors.forename: Joerg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Karsten
authors.initials: K
authors.lastname: Schulmann
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; 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