GNAS mutations in gastrointestinal tumors

• Project/Area Number: 26460429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Sekine Shigeki 国立研究開発法人国立がん研究センター, 中央病院, 医長 (10321879)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: GNAS / 消化管腫瘍 / 鋸歯状腺腫 / 胃上皮化生 / 幽門腺腺腫 / 十二指腸癌

Outline of Final Research Achievements

We identified frequent GNAS mutations in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum. GNAS mutations were exclusive to adenocarcinomas with gastric epithelial phenotypes, suggesting that gastric foveolar metaplasia and gastric heterotopia are precursors to these adenocarcinomas. Familial adenomatous polyposis (FAP)-associated pyloric gland adenomas were found to have frequent GNAS, KRAS, and APC mutations. This indicates that FAP-associated pyloric gland adenomas share common genetic features with sporadic cases despite their distinct clinical backgrounds. Mutational analyses of colorectal traditional serrated adenomas identified infrequent GNAS mutations as well as frequent RSPO fusions and RNF43 mutations as characteristic genetic alterations among colorectal polyps.

Research Products

• [Journal Article] Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion. (2017)
  • Author(s): Sekine S, Ogawa R, Saito S, Ushiama M, Shida D, Nakajima T, Taniguchi H, Hiraoka N, Yoshida T, Sugano K.
  • Journal Title: Histopathology Volume: 49 Issue: 4 Pages: 664-669
  • DOI: 10.1111/his.13104
  • Peer Reviewed
• [Journal Article] Mismatch repair deficiency commonly precedes adenoma formation in Lynch syndrome-associated colorectal tumorigenesis (2017)
  • Author(s): Sekine S, Mori T, Ogawa R, Tanaka M, Yoshida H, Taniguchi H, Nakajima T, Sugano K, Yoshida T, Kato M, Furukawa E, Ochiai A, Hiraoka N
  • Journal Title: Mod Pathol Volume: 印刷中 Issue: 8 Pages: 1144-1151
  • DOI: 10.1038/modpathol.2017.39
  • Peer Reviewed
• [Journal Article] Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma. (2016)
  • Author(s): Sekine S, Yamashita S, Tanabe T, Hashimoto T, Yoshida H, Taniguchi H, Kojima M, Shinmura K, Saito Y, Hiraoka N, Ushijima T, Ochiai A.
  • Journal Title: J Pathol Volume: 239 Issue: 2 Pages: 133-8
  • DOI: 10.1002/path.4709
  • Peer Reviewed
• [Journal Article] Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features (2015)
  • Author(s): Hashimoto T, Ogawa R, Matsubara A, Taniguchi H, Sugano K, Ushiama M, Yoshida T, Kanai Y, Sekine S
  • Journal Title: Histopathology Volume: in press Issue: 5 Pages: 689-98
  • DOI: 10.1111/his.12705
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Activating GNAS and KRAS mutations in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum (2015)
  • Author(s): Matsubara A, Ogawa R, Suzuki H, Oda I, Taniguchi H, Kanai Y, Kushima R, Sekine S
  • Journal Title: Br J Cancer Volume: 112 Issue: 8 Pages: 1398-404
  • DOI: 10.1038/bjc.2015.104
  • Peer Reviewed