Pathways of colorectal carcinogenesis from serrated lesions (especially from traditional serrated adenomas).

• Project/Area Number: 16K19097
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Hashimoto Taiki 国立研究開発法人国立がん研究センター, 中央病院, 医員 (40773875)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸腫瘍 / WNT / 分子病理学 / SSA/P / 癌 / RNF43 / RSPO / MLH1 / 大腸癌 / carcinogenesis / Wntシグナル / 病理学 / 遺伝子 / ゲノム / 臨床

Outline of Final Research Achievements

We identified frequent WNT pathway gene mutations in colorectal sessile serrated adenoma/polyps (SSA/Ps) with dysplasia. SSA/Ps with dysplasia exhibit distinct clinicopathological and molecular features depending on the MLH1 statuses. It is suggested that WNT pathway gene mutations are associated with the presence of dysplasia in SSA/Ps and SSA/Ps progress to carcinoma via two distinct pathways depending on the MLH1 statuses in the early stages of carcinogenesis.
We proposed a novel type of colorectal polyps characterized by mixed adenomatous and serrated features with KRAS mutation and RSPO fusion/overexpression.

Research Products

• [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: Modern Pathology Volume: 印刷中
  • 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] WNT pathway gene mutations are associated with the presence of dysplasia in colorectal sessile serrated adenoma/polyps (2017)
  • Author(s): Taiki Hashimoto, Satoshi Yamashita, Hiroshi Yoshida, Hirokazu Taniguchi, Toshikazu Ushijima, Tesshi Yamada, Yutaka Saito, Atsushi Ochiai, Shigeki Sekine, and Nobuyoshi Hiraoka
  • Journal Title: American Journal of Surgical Pathology Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Dysplasia を伴う大腸 SSA/P における WNT 関連遺伝子変異 (2017)
  • Author(s): 橋本 大輝
  • Organizer: 第 106回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2017-04-27
• [Presentation] Dysplasiaを伴う大腸SSA/PにおけるWNT関連遺伝子変異 (2017)
  • Author(s): 橋本 大輝、山下 聡、吉田 裕、谷口 浩和、牛島 俊和、山田 哲司、斎藤 豊、落合 淳志、関根 茂樹、平岡 伸介
  • Organizer: 第106回日本病理学会