title: Comprehensive mutation analysis in colorectal flat adenomas.
abstract: BACKGROUND
  Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phenotypes.
  
  
  METHODS
  A consecutive series of 106 flat and 93 polypoid adenomas was analyzed retrospectively for frequently occurring mutations in "hot spot" regions of KRAS, BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (β-catenin), EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high-throughput genotyping technique. Additionally, APC was analyzed using direct sequencing.
  
  
  RESULTS
  APC mutations were more frequent in polypoid adenomas compared to flat adenomas (48.5% versus 30.3%, respectively, p = 0.02). Mutations in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST-G) no differences were observed for any of the investigated genes.
  
  
  CONCLUSIONS
  The lower APC mutation rate in flat adenomas compared to polypoid adenomas suggests that disruption of the Wnt-pathway may occur via different mechanisms in these two phenotypes. Furthermore, in contrast to previous observations our results in this large well-defined sample set indicate that there is no significant association between the different morphological phenotypes and mutations in key genes of the RAS-RAF-MAPK pathway.
authors: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Quirinus J M
authors: QJ
authors: Voorham
authors: Beatriz
authors: B
authors: Carvalho
authors: Angela J
authors: AJ
authors: Spiertz
authors: Bart
authors: B
authors: Claes
authors: Sandra
authors: S
authors: Mongera
authors: Nicole C T
authors: NC
authors: van Grieken
authors: Heike
authors: H
authors: Grabsch
authors: Martin
authors: M
authors: Kliment
authors: Bjorn
authors: B
authors: Rembacken
authors: Mark A
authors: MA
authors: van de Wiel
authors: Philip
authors: P
authors: Quirke
authors: Chris J J
authors: CJ
authors: Mulder
authors: Diether
authors: D
authors: Lambrechts
authors: Manon
authors: M
authors: van Engeland
authors: Gerrit A
authors: GA
authors: Meijer
mesh_terms: D000236:Adenoma / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051176:beta Catenin / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins