title: Activating GNAS and KRAS mutations in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum.
abstract: BACKGROUND
  Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds.
  
  
  METHODS
  We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS, KRAS, and BRAF mutations.
  
  
  RESULTS
  Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS-mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation.
  
  
  CONCLUSIONS
  A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours.
authors: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors: A
authors: A
authors: Matsubara
authors: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors: R
authors: R
authors: Ogawa
authors: Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors: H
authors: H
authors: Suzuki
authors: Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors: I
authors: I
authors: Oda
authors: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors: H
authors: H
authors: Taniguchi
authors: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors: Y
authors: Y
authors: Kanai
authors: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors: R
authors: R
authors: Kushima
authors: 1] Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan [2] Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors: S
authors: S
authors: Sekine
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002864:Chromogranins; D004379:Duodenal Neoplasms / Q000235:genetics* / Q000473:pathology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D017422:Sequence Analysis, DNA; D013272:Stomach Diseases / Q000235:genetics / Q000473:pathology*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D002864:Chromogranins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins