Epigenomic analysis of gastrointestinal cancer stroma

• Project/Area Number: 23659400
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: SHINOMURA Yasuhisa 札幌医科大学, 医学部, 教授 (90162619)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Hiromu 札幌医科大学, 医学部, 助教 (20381254)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃癌 / 癌間質 / エピジェネティクス / メチル化 / 癌幹細胞

Research Abstract

We aimed to analyze epigenome alterations in gastrointestinal cancer cells,cancerstroma and background non-cancerous mucosa. By performing Methylated CpG Amplification (MCA)-microarray analysis and bisulfite-pyrosequencing analysis, we detected methylationof tumor-related genes, such as SFRP1 and miR-34b/c, in gastric cancer cells as well as cancer stroma. Moreover, we identified aberrant methylation of a candidate cancer-related gene, RASGRF1, in both gastric cancer cells and background non-cancerous mucosa. We also found that methylationof RASGRF1 could be a potential biomarker to assess gastric cancer risk.

Research Products

• [Journal Article] Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids (2013)
  • Author(s): Kato N, Yamamoto H, Adachi Y, Ohashi H, Taniguchi H, Suzuki H, Nakazawa M, Kaneto H, Sasaki S, Imai K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 19(11) Issue: 11 Pages: 1718-1727
  • DOI: 10.3748/wjg.v19.i11.1718
  • Peer Reviewed
• [Journal Article] Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer. (2012)
  • Author(s): Sukawa Y, Yamamoto H, Nosho K, Kunimoto H, Suzuki H, Adachi Y, Nakazawa M, Nobuoka T, Kawayama M,Mikami M, Matsuno T, Hasegawa T, Hirata K, Imai K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 18 Pages: 6577-6586
  • Peer Reviewed
• [Journal Article] Molecular dissection of premalignant colorectal lesions reveals early onset of the CpG island methylator phenotype (2012)
  • Author(s): Yamamoto E, Suzuki H, Yamano HO, Maruyama R, Nojima M, Kamimae S, Sawada T, Ashida M, Yoshikawa K, Kimura T, Takagi R, Harada T, Suzuki R, Sato A, Kai M, Sasaki Y, Tokino T, Sugai T, Imai K, Shinomura Y, Toyota M
  • Journal Title: Am J Pathol Volume: 181 Pages: 1847-1861
  • Peer Reviewed
• [Journal Article] Aberrant methylation of RASGRF1 is associated with an epigenetic field defect and increased risk of gastric cancer (2012)
  • Author(s): Takamaru H, Yamamoto E, Suzuki H, Nojima M, Maruyama R, Yamano HO, Yoshikawa K, Kimura T, Harada T, Ashida M, Suzuki R, Yamamoto H, Kai M, Tokino T, Sugai T, Imai K, Toyota M, Shinomura Y.
  • Journal Title: Cancer Prev Res Volume: 5 Pages: 1203-1212
  • Peer Reviewed
• [Journal Article] Model of translational cancer research in multiple myeloma (2012)
  • Author(s): Yasui H, Ishida T, Maruyama R, Nojima M, Ikeda H, Suzuki H, Hayashi T, Shinomura Y, Imai K
  • Journal Title: Cancer Sci Volume: 103 Pages: 1907-1912
  • Peer Reviewed
• [Journal Article] Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer (2012)
  • Author(s): Yamamoto H, Adachi Y, Taniguchi H, Kunimoto H, Nosho K, Suzuki H, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 18 Pages: 2745-2755
  • Peer Reviewed
• [Journal Article] Genome-wide analysis of DNA methylation identifies novel cancer-related genes in hepatocellular carcinoma (2012)
  • Author(s): Shitani M, Sasaki S, Akutsu N, Takagi H, Suzuki H, Nojima M, Yamamoto H, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y
  • Journal Title: Tumour Biol Volume: 33 Pages: 1307-1317
  • Peer Reviewed
• [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors (2012)
  • Author(s): Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, Nishida T, Bamba T, Kanda T, Ajioka Y, Taguchi T, Okahara S, Takahashi H, Nishida Y, Hosokawa M, Hasegawa T, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y
  • Journal Title: Cancer Res Volume: 72 Pages: 1126-1136
  • NAID: 10031131121
  • Peer Reviewed
• [Journal Article] Emerging links between epigenetic alterations and dysregulation of noncoding RNAs in cancer (2012)
  • Author(s): Maruyama R, Suzuki H, Yamamoto E, Imai K, Shinomura Y
  • Journal Title: Tumour Biol Volume: 33 Pages: 277-85
  • Peer Reviewed
• [Journal Article] A novel pit pattern identifies the precursor of colorectal cancer derived from sessile serrated adenoma (2012)
  • Author(s): Kimura T, Yamamoto E, Yamano HO, Suzuki H, Kamimae S, Nojima M, SawadaT, Ashida M, Yoshikawa K, Takagi R, Kato R, Harada T, Suzuki R, Maruyama R, Kai M, Imai K, Shinomura Y, Sugai T, Toyota M
  • Journal Title: Am J Gastroenterol Volume: 107 Pages: 460-469
  • Peer Reviewed
• [Journal Article] IGF-I receptor expression is associated with aggressive phenotypes and has therapeutic activity in biliary tract cancers (2012)
  • Author(s): Ohashi H, Adachi Y, Yamamoto H, Taniguchi H, Nosho K, Suzuki H, Arimura Y, Imai K, Carbone DP, Shinomura Y
  • Journal Title: Cancer Sci Volume: 103 Pages: 252-261
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation associatedwith aggressiveness of gastrointestinal stromal tumour (2012)
  • Author(s): Okamoto Y, Sawaki A, Ito S, Nishida T, Takahashi T, Toyota M, Suzuki H, Shinomura Y, Takeuchi I, Shinjo K, An B, Ito H, Yamao K, Fujii M, Murakami H, Osada H, Kataoka H, Joh T, Sekido Y, Kondo Y
  • Journal Title: Gut Volume: 61 Pages: 392-401
  • Peer Reviewed
• [Journal Article] Aberrant Methylation of RASGRF1 Is Associated with an Epigenetic Field Defect and Increased Risk of Gastric Cancer. (2012)
  • Author(s): Takamaru H, Yamamoto E, Suzuki H.
  • Journal Title: Cancer Prev Res (Phila) Volume: 5(10) Issue: 10 Pages: 2012-2012
  • DOI: 10.1158/1940-6207.capr-12-0056
  • Peer Reviewed
• [Journal Article] Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer (2012)
  • Author(s): Sukawa Y, Yamamoto H (他11名), Nosho K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 18 Issue: 45 Pages: 6577-6586
  • DOI: 10.3748/wjg.v18.i45.6577
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation associated with aggressiveness of gastrointestinal stromal tumour (2012)
  • Author(s): Okamoto Y
  • Journal Title: Gut Volume: 61 Issue: 3 Pages: 392-401
  • DOI: 10.1136/gut.2011.241034
  • Peer Reviewed
• [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors (2012)
  • Author(s): Takeshi Niinuma
  • Journal Title: Cancer research Volume: 72 Issue: 5 Pages: 1126-36
  • DOI: 10.1158/0008-5472.can-11-1803
  • Peer Reviewed
• [Journal Article] The efficacy of IGF-I receptor monoclonal antibody against human gastrointestinal carcinomas is independent of k-ras mutation status (2011)
  • Author(s): Ii M, Li H, Adachi Y, Yamamoto H, Ohashi H, Taniguchi H, Arimura Y, Carbone DP, Imai K, Shinomura Y
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 5048-5059
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor-I receptor blockade reduces tumor angiogenesis and enhances the effects of bevacizumab for a human gastric cancer cell line, MKN45 (2011)
  • Author(s): Li H, Adachi Y, Yamamoto H, Min Y, Ohashi H, Ii M, Arimura Y, Endo T, Lee CT, Carbone DP, Imai K, Shinomura Y
  • Journal Title: Cancer Volume: 117 Pages: 3135-3147
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer (2011)
  • Author(s): Suzuki H, Takatsuka S, Akashi H, Yamamoto E, Nojima M, Maruyama R, Kai M, Yamano HO, Sasaki Y, Tokino T, Shinomura Y, Imai K, Toyota M
  • Journal Title: Cancer Res Volume: 71 Pages: 5646-5658
  • NAID: 130004436468
  • Peer Reviewed
• [Journal Article] Co-expression of laminin β3 and γ2 chains and epigenetic inactivation of laminin α3 chain in gastric cancer (2011)
  • Author(s): Ii M, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Ohashi H, Tanuma T, Sukawa Y, Suzuki H, Sasaki S, Imai K, Shinomura Y
  • Journal Title: Int J Oncol Volume: 39 Pages: 593-599
  • Peer Reviewed
• [Journal Article] Interferon-α/β and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo (2011)
  • Author(s): Sasaki S, Ishida T, Toyota M, Ota A, Suzuki H, Takaoka A, Yasui H, Yamamoto H, Takagi H, Maeda M, Seito T, Tsujisaki M, Shinomura Y, Imai K
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors (2011)
  • Author(s): Kamimae S, Yamamoto E, Yamano HO, Nojima M, Suzuki H, Ashida M, Hatahira T, Sato A, Kimura T, Yoshikawa K, Harada T, Hayashi S, Takamaru H, Maruyama R, Kai M, Nishiwaki M, Sugai T, Sasaki Y, Tokino T, Shinomura Y, Imai K, Toyota M
  • Journal Title: Cancer Prev Res Volume: 4 Pages: 674-683
  • Peer Reviewed
• [Journal Article] Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis (2011)
  • Author(s): Hizaki K, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Tanuma T, Kato N, Sukawa Y, Sanchez JV, Suzuki H, Sasaki S, Imai K, Shinomura Y
  • Journal Title: Mod Pathol Volume: 24 Pages: 876-884
  • Peer Reviewed
• [Journal Article] Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis (2011)
  • Author(s): Hizaki K, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Tanuma T, Kato N, Sukawa Y, Sanchez JV, Suzuki H, Sasaki S, Imai K, Shinomura Y
  • Journal Title: Mod Pathol Volume: 24 Issue: 6 Pages: 876-884
  • DOI: 10.1038/modpathol.2011.10
  • Peer Reviewed
• [Presentation] 篠村恭久.miR-34b/cの異常メチル化は胃癌の異時性多発リスクに関与する (2012)
  • Author(s): 鈴木亮,山本英一郎,鈴木拓,丸山玲緒,能正勝彦,山本博幸,野島正寛,甲斐正広,山野泰穂,菅井有,今井浩三
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] microRNA-34b/cの異常メチル化は胃癌の異時性多発リスクに関与する (2012)
  • Author(s): 鈴木亮,山本英一郎,鈴木拓,野島正寛,丸山玲緒,能正勝彦,山本博幸,甲斐正広,山野泰穂,菅井有,今井浩三,篠村恭久
  • Organizer: 第32回日本分子腫瘍マーカー研究会
  • Place of Presentation: 札幌
• [Presentation] GISTの悪性度マーカーおよび治療標的としてのnon-coding RNA (2012)
  • Author(s): 新沼猛,鈴木拓,野島正寛,高丸博之,山本英一郎,能正勝彦,山本博幸,篠村恭久
  • Organizer: 第8回日本消化管学会総会学術集会
  • Place of Presentation: 仙台
• [Presentation] 胃癌におけるPI3K-Akt経路に関わるHER2発現、PIK3CA変異、EBV感染の臨床病理および分子学的意義に関する検討 (2012)
  • Author(s): 須河恭敬
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] miR-34b/cの異常メチル化は胃癌の異時性多発リスクに関与する (2012)
  • Author(s): 鈴木 亮
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 胃癌におけるPI3K-Akt経路下流シグナル異常活性化に関わる因子に関する検討 (2012)
  • Author(s): 須河恭敬
  • Organizer: 第20回日本消化器関連学会週間(JDDW)
  • Place of Presentation: 神戸
• [Presentation] 胃癌におけるエピジェネティックな遺伝子異常の網羅的解析 (2012)
  • Author(s): 高丸博之、鈴木拓、山本英一郎、神前正幸、新沼猛、丸山玲緒、豊田実、篠村恭久
  • Organizer: 第8回日本消化管学会総会学術集会
  • Place of Presentation: 仙台
• [Presentation] 消化管間質腫瘍におけるmicroRNA発現プロファイル解析 (2011)
  • Author(s): 新沼猛,鈴木拓,野島正寛,高丸博之,能正勝彦,山本博幸,豊田実,篠村恭久
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡
• [Presentation] DNAメチル化異常の網羅的な解析による新規胃癌関連遺伝子の検索 (2011)
  • Author(s): 高丸博之,鈴木拓,山本英一郎,新沼猛,山本博幸,有村佳昭,豊田実,篠村恭久
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡
• [Presentation] 胃癌におけるゲノムワイドな低メチル化と染色体不安定性 (2011)
  • Author(s): 鈴木亮,山本英一郎,鈴木拓,丸山玲緒,山野泰穂,今井浩三,豊田実,篠村恭久
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 胃癌におけるエピジェジェティックな遺伝子異常の網羅的解析 (2011)
  • Author(s): 高丸博之,鈴木拓,山本英一郎,丸山玲緒,神前正幸,新沼猛,青木由佳,澤田武,豊田実,篠村恭久
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 胃癌におけるエピジェネティックな遺伝子異常の網羅的解析 (2011)
  • Author(s): 高丸博之、鈴木拓、山本英一郎、丸山玲緒、神前正幸、新沼猛、青木由佳、澤田武、豊田実、篠村恭久
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 消化管間質腫瘍におけるmicroRNA発現プロファイル解析 (2011)
  • Author(s): 新沼猛、鈴木 拓、野島正寛、高丸博之、能正勝彦、山本博幸、豊田実、篠村恭久
  • Organizer: 第19回日本消化器関連学会週間
  • Place of Presentation: 福岡