title: APC and CTNNB1 mutations in a large series of sporadic colorectal carcinomas stratified by the microsatellite instability status.
abstract: BACKGROUND
  Adenomatous polyposis coli (APC) and beta-catenin (encoded by CTNNB1) are important components in the WNT signalling pathway, a pathway altered in nearly all colorectal tumours. Conflicting results are reported on whether APC mutations are less common in tumours with a high degree of microsatellite instability (MSI-H) than in microsatellite stable (MSS) ones, and whether mutations in the regulatory domain of CTNNB1 substitute for APC mutations in the MSI-H tumours.
  
  
  METHODS
  A consecutive series of 218 primary colorectal carcinomas, stratified by MSI status, were analysed for mutations in the APC gene (by the protein truncation test) and in the CTNNB1 gene (by single-strand conformation polymorphism).
  
  
  RESULTS
  APC mutations detected in 66% of the patients were significantly more frequent in the MSS and MSI-L (low) tumours than in the MSI-H tumour group (P < 0.001). The MSI-H tumours tended to have more frameshift mutations than the MSS/MSI-L tumours. The majority of the APC mutations were located in the mutation cluster region (MCR). Patients that had lost all beta-catenin binding sites of the APC gene showed a shorter survival time than patients who retained some or all of these binding sites (P = 0.045). Two mutations were found in the CTNNB1 gene, but neither of them was located in the regulatory domain in exon 3.
  
  
  CONCLUSIONS
  This study confirms that APC mutations are less frequent in MSI-H tumours than in MSS and MSI-L tumours. However, CTNNB1 mutations do not substitute for APC mutations in MSI-H tumours in these Norwegian patients.
authors.affiliation: Institute of Forensic Medicine, The National Hospital, University of Oslo, Norway. tone.lovig@labmed.uio.no
authors.forename: T
authors.initials: T
authors.lastname: Løvig
authors.forename: G I
authors.initials: GI
authors.lastname: Meling
authors.forename: C B
authors.initials: CB
authors.lastname: Diep
authors.forename: L
authors.initials: L
authors.lastname: Thorstensen
authors.forename: S
authors.initials: S
authors.lastname: Norheim Andersen
authors.forename: R A
authors.initials: RA
authors.lastname: Lothe
authors.forename: T O
authors.initials: TO
authors.lastname: Rognum
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D008934:Mitogens / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin