Identification of histon modifications to predict colorectal cancer risk

• Project/Area Number: 15K18431
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Sapporo Medical University
• Principal Investigator: Harada Taku 札幌医科大学, 医学部, 研究員 (60468030)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 大腸がん / エピジェネティクス / DNAメチル化 / ヒストン修飾 / 大腸鋸歯状病変 / メチル化

Outline of Final Research Achievements

We found that genes marked by bivalent chromatin domain in ESCs are significantly associated with H3K27me3 in noncancerous colonic mucosa of patients with CIMP-positive tumors. Moreover, a large number of genes marked by H3K27me3 in noncancerous colonic mucosa were specifically methylated in CIMP-positive CRCs. In contrast, such enrichment of H3K27me3 was not observed in colonic mucosa of patients with CIMP-negative tumors. We identified a series of genes, which were marked by H3K27me3 in the background colonic mucosa of CIMP-positive CRCs and were aberrantly methylated in CIMP-positive CRCs. Our results suggest that H3K27me3 may act as a pre-mark in the noncancerous colon mucosa of patients at a high risk of CIMP-positive cancer.

Research Products

• [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: - Pages: 1743-1752
  • DOI: 10.1002/mc.22631
  • Peer Reviewed / Open Access
• [Journal Article] TET1 Depletion Induces Aberrant CpG Methylation in Colorectal Cancer Cells (2016)
  • Author(s): Kai M, Niinuma T, Kitajima H, Yamamoto E, Harada T, Aoki H, Maruyama R, Toyota M, Sasaki Y, Sugai T, Tokino T, Nakase H, Suzuki H.
  • Journal Title: PLoS One. Volume: 11
  • DOI: 10.1371/journal.pone.0168281
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations. (2016)
  • Author(s): Sawada T, Yamamoto E, Yamano HO, Nojima M, Harada T, Maruyama R, Ashida M, Aoki H, Matsushita HO, Yoshikawa K, Harada E, Tanaka Y, Wakita S, Niinuma T, Kai M, Eizuka M, Sugai T, Suzuki H.
  • Journal Title: Oncotarget. Volume: 7 Pages: 35106-35108
  • DOI: 10.18632/oncotarget.9044
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenetic silencing of NTSR1 is associated with lateral and noninvasive growth of colorectal tumors. (2015)
  • Author(s): Kamimae S, Yamamoto E, Kai M, Niinuma T, Yamano HO, Nojima M, Yoshikawa K, Kimura T, Takagi R, Harada E, Harada T, Maruyama R, Sasaki Y, Tokino T, Shinomura Y, Sugai T, Imai K, Suzuki H
  • Journal Title: Oncotarget. Volume: 6 Pages: 29975-29990
  • DOI: 10.18632/oncotarget.5034
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 腸管洗浄液のメチル化解析による大腸癌診断法の検討 (2015)
  • Author(s): 原田 拓,鈴木 拓,山野 泰穂
  • Organizer: JDDW 2015
  • Place of Presentation: グランドプリンスホテル新高輪（東京、品川）
  • Year and Date: 2015-10-08
• [Presentation] BRAF変異を有する進行大腸癌の内視鏡的特徴 (2015)
  • Author(s): 檜森亮吾, 山野泰穂, 松下弘雄, 吉川健二郎, 原田英嗣, 高木亮, 田中義人, 中岡宙子, 吉田優子, 青木敬則, 山本英一郎, 鈴木拓, 菅井有
  • Organizer: 第８９回日本消化器内視鏡学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-05-29