title: Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum.
abstract: Gastric and duodenal adenomas exhibit a significant morphological and phenotypical diversity and are classified into intestinal-type, foveolar-type and pyloric gland adenomas. We analysed the mutations in GNAS, KRAS, BRAF and CTNNB1 and the expressions of mismatch repair (MMR) proteins in 80 gastric and 32 duodenal adenomas with histologically distinct subtypes, as well as in 71 gastric adenocarcinomas. Activating GNAS mutations were found in 22 of the 35 pyloric gland adenomas (PGAs; 63%) but in none of the foveolar-type or intestinal-type adenomas or the adenocarcinomas. Fourteen PGAs (41%), two foveolar-type adenomas (9%), five intestinal-type adenomas (9%) and one adenocarcinoma (1%) had KRAS mutations. BRAF mutations were absent in all the adenomas and adenocarcinomas that were examined. CTNNB1 mutations were only found in two intestinal-type adenomas (4%). Notably, 13 of the 14 KRAS-mutated gastric and duodenal PGAs had concurrent GNAS mutations. The loss of the MMR proteins, which is indicative of microsatellite instability, was observed in one PGA (3%), 12 foveolar-type adenomas (52%), one intestinal-type adenoma (2%) and five adenocarcinomas (7%). These observations indicate that each histological subtype of gastric and duodenal adenomas has a distinct genetic background. In particular, the present study identified the frequent presence of activating GNAS mutations, which are often associated with KRAS mutations, as a characteristic genetic feature of PGAs of the stomach and duodenum.
authors.affiliation: Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsubara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Reiko
authors.initials: R
authors.lastname: Ogawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002864:Chromogranins; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004379:Duodenal Neoplasms / Q000235:genetics* / Q000473:pathology; D004386:Duodenum / Q000473:pathology; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005753:Gastric Mucosa / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002864:Chromogranins; D004268:DNA-Binding Proteins; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D000251:Adenosine Triphosphatases; C406732:GNAS protein, human; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D045643:DNA Repair Enzymes