Frequent activating GNAS mutations in villous adenoma of the colorectum

Masayoshi Yamada, Shigeki Sekine, Reiko Ogawa, Hirokazu Taniguchi, Ryoji Kushima, Hitoshi Tsuda, Yae Kanai

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)113-118
Number of pages6
JournalJournal of Pathology
Issue number1
Publication statusPublished - 2012 Sept
Externally publishedYes


  • BRAF
  • GNAS
  • KRAS
  • colorectum
  • villous adenoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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