Significance of Wnt-signal and hedgehog-signal pathways and GNS mutation in carcinogenesis of gastric adenocarcinoma of fundic gland type

• Project/Area Number: 26460428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Juntendo University
• Principal Investigator: YAO Takashi 順天堂大学, 医学部, 教授 (20243933)
• Co-Investigator(Kenkyū-buntansha): 齋藤 剛 順天堂大学, 医学部, 准教授 (80439736)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃底腺型胃癌 / GNAS / Hedgehogシグナル伝達系 / Wntシグナル伝達系 / Wnt/β-catenin signal / GNA / Sonic hegdehog signal / Hhシグナル伝達系 / Wnt/β-catenin signal系 / KRAS

Outline of Final Research Achievements

From the above results, it was re-confirmed that the GNAS gene mutation is involved in the carcinogenesis or progression of gastric fundus gland type gastric cancer, and it has been shown for the first time that KRAS and BRAF gene mutations are not related to gastric fundus gland type gastric cancer It was. It is suggested that suppression of Sonic hedgehog signal may be involved in the development or progression of gastric fundus gland type gastric cancer in addition to activation of Wnt / β-catenin signal (particularly methylation is involved in particular) and GNAS gene mutation It was done.

Research Products

• [Journal Article] Epigenetic regulation of Wnt/β-catenin signal-associated genes in gastric neoplasia of the fundic gland (chief cell-predominant) type (2017)
  • Author(s): Murakami T, Hitomi H, Yao T, Saito T, Watanabe S.
  • Journal Title: Patrol Int Volume: 67 Issue: 3 Pages: 147-155
  • DOI: 10.1111/pin.12509
  • Peer Reviewed
• [Journal Article] Expression of adipophilin in gastric epithelial neoplasia is associated with intestinal differentiation and discriminates between adenoma and adenocarcinoma. (2016)
  • Author(s): Gushima R, Yao T, Kurisaki-Arakawa A, Hara K, Hayashi T, Fukumura Y, Saito T, Arakawa A, Sasaki Y
  • Journal Title: Virchow Arch Volume: 468 Issue: 2 Pages: 169-177
  • DOI: 10.1007/s00428-015-1870-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinicopathologic and immunohistochemical characteristics of gastric adenocarcinoma with enteroblastic differentiation: a study of 29 cases. (2016)
  • Author(s): Murakami T, Yao T, Mitomi H, Morimoto T, Ueyama H, Maatsumoto K, Satio T, Msada T, Nagahara A, Watanabe S
  • Journal Title: Gastric cancer Volume: 19 Issue: 2 Pages: 498-507
  • DOI: 10.1007/s10120-015-0497-9
  • NAID: 40020835813
  • Peer Reviewed
• [Journal Article] utation spectrum in the Wnt/β-catenin signaling pathway in gastric fundic gland-associated neoplasms/polyps. (2015)
  • Author(s): Lee S-Y, Saito T, Mitomi H, Hidaka Y, Murakami T, Nomura R, Watanabe S, Yao T
  • Journal Title: Virchow Arch Volume: 467 Issue: 1 Pages: 27-38
  • DOI: 10.1007/s00428-015-1753-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] GNAS mutation as an alternative mechanism of activation of the Wnt/β-catenin signaling pathway in gastric adenocarcinoma of the fundic gland type. (2014)
  • Author(s): Nomura R, Saito T, Mitomi H, Hidaka Y, Lee S-Y, Watanabe S, Yao T
  • Journal Title: Human Pathology Volume: 45 Issue: 12 Pages: 2488-2496
  • DOI: 10.1016/j.humpath.2014.08.016
  • Peer Reviewed
• [Journal Article] Gastric adenocarcinoma of the fundic gland type (chief cell predominant type). (2014)
  • Author(s): Ueyama H, Matsumoto K, Nagahara A, Hayashi T, Yao T, Watanabe S.
  • Journal Title: Endoscopy Volume: 46 Issue: 02 Pages: 153-157
  • DOI: 10.1055/s-0033-1359042
  • Peer Reviewed
• [Presentation] Gastric adenocarcinoma of fundic gland type. A new entity. (2016)
  • Author(s): Yao T, Ueyama H.
  • Organizer: Nottingham Pathology 2016
  • Place of Presentation: Nottingham
  • Int'l Joint Research / Invited