WNT pathway-related genetic alterations in colorectal tumors

• Project/Area Number: 17K08711
• 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): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: WNT / 鋸歯状病変 / 大腸ポリープ / 大腸癌

Outline of Final Research Achievements

We conducted histological and molecular analyses of traditional serrated adenomas and showed that genetic alterations leading to activation of WNT and MAPK pathways play critical roles in their development. We also analyzed various types of serrated lesions for their molecular features, and showed the role of WNT pathway-related gene alterations in the serrated pathway of colorectal tumorigenesis.

Academic Significance and Societal Importance of the Research Achievements

近年、新たな大腸発癌経路として注目されている、鋸歯状腺腫を中心とした大腸鋸歯状病変の分子病理学的解析を行い、その遺伝子変異の多様性と形態との相関を明らかにした。特にWNT経路を中心とする分子異常の鋸歯状経路における意義が明らかになったことで、これらの病変を前駆とする大腸癌との関連などの、大腸癌発生過程をより詳細に理解することが期待される。

Research Products

• [Journal Article] Clinicopathological and molecular correlations in traditional serrated adenoma (2020)
  • Author(s): Sekine Shigeki、Yamashita Satoshi、Yamada Masayoshi、Hashimoto Taiki、Ogawa Reiko、Yoshida Hiroshi、Taniguchi Hirokazu、Kojima Motohiro、Ushijima Toshikazu、Saito Yutaka
  • Journal Title: Journal of Gastroenterology Volume: 55 Issue: 4 Pages: 418-427
  • DOI: 10.1007/s00535-020-01673-z
  • Peer Reviewed
• [Journal Article] Clinicopathologic and Molecular Characteristics of Familial Adenomatous Polyposis?associated Traditional Serrated Adenoma (2020)
  • Author(s): Okamura Takuma、Hashimoto Taiki、Naka Tomoaki、Yoshida Teruhiko、Tanabe Noriko、Ogawa Reiko、Yamada Masayoshi、Saito Yutaka、Yatabe Yasushi、Sekine Shigeki
  • Journal Title: American Journal of Surgical Pathology Volume: Publish Ahead of Print Issue: 9 Pages: 1282-1289
  • DOI: 10.1097/pas.0000000000001502
  • Peer Reviewed
• [Journal Article] Reappraisal of the genetic heterogeneity of sessile serrated adenoma/polyp (2018)
  • Author(s): Cho H, Hashimoto T, Yoshida H, Taniguchi H, Ogawa R, Mori T, Hiraoka N, Saito Y, Sekine S
  • Journal Title: Histopathology Volume: 73 Issue: 4 Pages: 672-80
  • DOI: 10.1111/his.13688
  • Peer Reviewed
• [Journal Article] Superficially serrated adenoma: a proposal for a novel subtype of colorectal serrated lesion (2018)
  • Author(s): Hashimoto T, Tanaka Y, Ogawa R, Mori T, Yoshida H, Taniguchi H, Hiraoka N, Kojima M, Oono Y, Saito Y, Sekine S
  • Journal Title: Mod Pathol Volume: 31 Issue: 10 Pages: 1588-98
  • DOI: 10.1038/s41379-018-0069-8
  • Peer Reviewed
• [Journal Article] WNT Pathway Gene Mutations Are Associated With the Presence of Dysplasia in Colorectal Sessile Serrated Adenoma/Polyps (2017)
  • Author(s): Hashimoto Taiki、Yamashita Satoshi、Yoshida Hiroshi、Taniguchi Hirokazu、Ushijima Toshikazu、Yamada Tesshi、Saito Yutaka、Ochiai Atsushi、Sekine Shigeki、Hiraoka Nobuyoshi
  • Journal Title: The American Journal of Surgical Pathology Volume: 41 Issue: 9 Pages: 1188-1197
  • DOI: 10.1097/pas.0000000000000877
  • Peer Reviewed
• [Journal Article] Intramucosal colorectal carcinoma with invasion of the lamina propria: a study by the Japanese Society for Cancer of the Colon and Rectum (2017)
  • Author(s): Kojima Motohiro、Shimazaki Hideyuki、Iwaya Keiichi、Nakamura Takahiro、Kawachi Hiroshi、Ichikawa Kazuhito、Sekine Shigeki、Ishiguro Shingo、Shimoda Tadakazu、Kushima Ryoji、Yao Takashi、Fujimori Takahiro、Hase Kazuo、Watanabe Toshiaki、Sugihara Kenichi、Lauwers Gregory Y.、Ochiai Atsushi
  • Journal Title: Human Pathology Volume: 66 Pages: 230-237
  • DOI: 10.1016/j.humpath.2017.04.031
  • Peer Reviewed
• [Journal Article] Adenocarcinoma of the colon presenting as a submucosal tumor (2017)
  • Author(s): Cho Hourin、Sekine Shigeki、Sekiguchi Masau
  • Journal Title: Digestive Endoscopy Volume: 30 Issue: 1 Pages: 114-115
  • DOI: 10.1111/den.12949
  • Peer Reviewed