title: Report on de-novo mutation in the MSH2 gene as a rare event in hereditary nonpolyposis colorectal cancer.
abstract: OBJECTIVE
  Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant predisposition for early-onset colorectal cancer and associated tumour types caused by mutations in DNA mismatch repair genes, mainly MLH1 and MSH2. The Amsterdam criteria, stressing familial tumour events, as well as the less stringent Bethesda criteria, help to raise suspicion of HNPCC.
  
  
  RESULTS
  Mutation screening in a colon cancer patient of young age but negative family history revealed the MSH2 splice site mutation c.2006-2A>G. This mutation was present in all three germ cell layers in the patient, but absent in her biological parents, reporting the second case of de-novo germline mutation in MSH2.
  
  
  CONCLUSIONS
  Our findings suggest that at least in approximately 1% of mutation-positive cases, a de-novo event might be involved. The identification of a newly evolved rare mutation calls for alertness and encourages the application of the Bethesda guidelines and certain clinical and histopathological features to define candidates for HNPCC gene mutation screening despite a negative family history.
authors.affiliation: Department of Internal Medicine, Campus Innenstadt, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Morak
authors.forename: Andreas
authors.initials: A
authors.lastname: Laner
authors.forename: Michael
authors.initials: M
authors.lastname: Scholz
authors.forename: Trisari
authors.initials: T
authors.lastname: Madorf
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
mesh_terms: D000328:Adult; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: D018076:DNA, Complementary; D004273:DNA, Neoplasm; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein