title: Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features.
abstract: OBJECTIVE
  Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome caused by a germline APC mutation. A recent study showed the enrichment of pyloric gland adenomas (PGAs) of the stomach, in addition to fundic gland polyps (FGPs) and foveolar-type adenomas (FAs), in patients with FAP. In the present study, we analysed the genetic alterations in these FAP-associated gastric lesions.
  
  
  RESULTS
  Mutational statuses of GNAS and KRAS, which are frequently mutated in sporadic PGAs, as well as those of APC, were examined in PGAs, FAs and FGPs in patients with FAP using Sanger sequencing. Our analysis identified GNAS mutations in five of six PGAs (83%), but in none of the three FAs or the 40 FGPs examined. KRAS mutations were identified in four PGAs (67%), one FA (33%) and one FGP (3%). Somatic truncating APC mutations were found in all PGAs (100%), two FAs (67%) and 14 FGPs (47%). We additionally analysed sporadic PGAs of the stomach and duodenum and identified truncating APC mutations in 11 of 25 lesions (44%).
  
  
  CONCLUSIONS
  FAP-associated and sporadic PGAs not only show similar morphologies, but also share common genetic aberrations, including mutations of GNAS, KRAS and APC.
authors.affiliation: Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsubara
authors.affiliation: Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Sugano
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Mineko
authors.initials: M
authors.lastname: Ushiama
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan.|Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
mesh_terms: D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D002864:Chromogranins; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D005753:Gastric Mucosa / Q000473:pathology*; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D002864:Chromogranins; C117307:KRAS protein, human; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras)
keywords: APC; GNAS; KRAS; familial adenomatous polyposis; fundic gland polyp; pyloric gland adenoma