Identification of enhancer regions associated with carcinogensis of colorectal cancer

• Project/Area Number: 17K09387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Harada Taku 札幌医科大学, 医学部, 研究員 (60468030)
• Co-Investigator(Kenkyū-buntansha): 山本 英一郎 札幌医科大学, 医学部, 講師 (60567915)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 大腸がん / メチル化 / がん遺伝子 / エピジェネティクス / DNAメチル化 / ヒストン修飾

Outline of Final Research Achievements

We aimed to identify enhancer regions, epigenetic alterations of which are associated with carcinogenesis of colorectal cancer (CRC). Our genome-wide methylation analysis of normal colon mucosa reveal one enhancer region increased DNA methylation level in normal colon of high risk patient of CRC. Several oncogenes were located in this region and aberrant DNA methylation was associated with expression of these genes. Our result suggest that DNA methylation of enhancer regions were useful for predicting carcinogenesis of CRC.

Academic Significance and Societal Importance of the Research Achievements

大腸がん死を減らすためには、予防、早期発見が重要である。発癌リスクにより層別化し効率的に大腸内視鏡検査を施行し、前癌病変、早期大腸癌を同定し、内視鏡的に切除することは極めて重要である。本研究では疫学的に発がんハイリスクと考えられている症例において、癌遺伝子の発現上昇と関連するメチル化異常を同定した。メチル異常により、発がんリスクを層別化することが可能となれば大腸内視鏡検査を効率的に施行し、また大腸がんの予防、早期発見に有用であると考える。

Research Products

• [Journal Article] Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection (2020)
  • Author(s): Suzuki Yuichiro、Tanuma Tokuma、Nojima Masanori、Sudo Gota、Akahonai Masakazu、Hamamoto Hidetaka、Aoki Hironori、Harada Taku、Katanuma Akio、Nakase Hiroshi
  • Journal Title: Gastrointestinal Endoscopy Volume: 91 Issue: 1 Pages: 185-190
  • DOI: 10.1016/j.gie.2019.08.042
  • Peer Reviewed
• [Journal Article] Surface microstructures are associated with mutational intratumoral heterogeneity in colorectal tumors (2018)
  • Author(s): Harada T、Yamamoto E、Yamano HO、Aoki H、Matsushita HO、Yoshikawa K、Takagi R、Harada E、Tanaka Y、Yoshida Y、Eizuka M、Yorozu A、Sudo G、Kitajima H、Niinuma T、Kai M、Sasaki Y、Tokino Takashi、Sugai T、Nakase H、Suzuki H
  • Journal Title: Journal of Gastroenterology Volume: 53 Issue: 12 Pages: 1241-1252
  • DOI: 10.1007/s00535-018-1481-z
  • Peer Reviewed / Open Access
• [Journal Article] Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway. (2018)
  • Author(s): Aoki H, Yamamoto E, Yamano HO, Sugai T, Kimura T, Tanaka Y, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Nakaoka M, Yoshida Y, Harada T, Sudo G, Eizuka M, Yorozu A, Kitajima H, Niinuma T, Kai M, Nojima M, Suzuki H, Nakase H.
  • Journal Title: Dig Dis Sci. Volume: 15 Issue: 7 Pages: 1920-1928
  • DOI: 10.1007/s10620-018-5016-5
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic silencing of diacylglycerol kinase gamma in colorectal cancer. (2017)
  • Author(s): Kai M, Yamamoto E, Sato A, Yamano HO, Niinuma T, Kitajima H, Harada T, Aoki H, Maruyama R, Toyota M, Hatahira T, Nakase H, Sugai T, Yamashita T, Toyota M, Suzuki H.
  • Journal Title: Mol Carcinog Volume: - Issue: 7 Pages: 1743-1752
  • DOI: 10.1002/mc.22631
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors. (2017)
  • Author(s): Niinuma T, Kai M, Kitajima H, Yamamoto E, Harada T, Maruyama R, Nobuoka T, Kanda T, Hasegawa T, Tokino T, Sugai T, Shimomura Y, Nakase H, Suzuki H
  • Journal Title: Oncology Letters Volume: 14 Pages: 5703-5710
  • DOI: 10.3892/ol.2017.6911
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer. (2017)
  • Author(s): Aoki H, Yamamoto E, Takasawa A, Niinuma T, Yamano HO, Harada T, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Tanaka Y, Yoshida Y, Aoyama T, Eizuka M, Yorozu A, Kitajima H, Kai M, Sawada N, Sugai T, Nakase H, Suzuki H.
  • Journal Title: Oncotarget. Volume: 9 Issue: 4 Pages: 4707-4721
  • DOI: 10.18632/oncotarget.23523
  • Peer Reviewed / Open Access