title: Frequent activating GNAS mutations in villous adenoma of the colorectum.
abstract: To elucidate the role of GNAS mutations in colorectal tumourigenesis, we performed a mutation analysis in a total of 234 colorectal tumours, including adenomas, serrated lesions and adenocarcinomas. Activating GNAS mutations were found in 20 of the 24 villous adenomas (83%) but were absent in all the other tumours, except for one tubulovillous adenoma (3%) and two adenocarcinomas (3%). KRAS and BRAF mutations were always mutually exclusive. KRAS mutations were frequent in villous (67%) and tubulovillous (60%) adenomas but were rare or absent in tubular adenomas (6%) and serrated lesions, including hyperplastic polyps, sessile serrated polyps/sessile serrated lesions and traditional serrated adenomas (0-9%). BRAF mutations were found in four villous adenomas (17%) and in the large majority of serrated lesions (81-92%), but were absent in tubular and tubulovillous adenomas. Seventeen villous adenomas (71%) harboured GNAS mutations concomitantly with KRAS or BRAF mutations. Immunohistochemically, all the villous adenomas retained mismatch repair protein expression, suggesting that they are microsatellite-stable. The current study showed that the presence of activating GNAS mutations, in association with KRAS or BRAF mutations, is a characteristic genetic feature of colorectal villous adenoma.
authors.affiliation: Pathology and Clinical Laboratory, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
authors.forename: Reiko
authors.initials: R
authors.lastname: Ogawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D018253:Adenoma, Villous / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002864:Chromogranins; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; 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); D018631:ras Proteins / Q000235:genetics
chemical_list: D002864:Chromogranins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins