Development of novel gastrointestinal cancer diagnostic system based on large epige-nome analysis.

• Project/Area Number: 23240129
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: The University of Tokyo
• Principal Investigator: IMAI Kohzoh 東京大学, 医科学研究所, 特任教授 (60117603)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Hiromu 札幌医科大学, 医学部, 教授 (20381254) ; TANIGUCHI Hiroaki 東京大学, 医科学研究所, 特任准教授 (90563289)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000); Fiscal Year 2013: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000); Fiscal Year 2012: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000); Fiscal Year 2011: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000)
• Keywords: 胃癌 / 大腸癌 / 肝癌 / エピゲノム / ＤＮＡメチル化 / バイオマーカー / がん / マイクロＲＮＡ / 癌 / ゲノム / トランスレーショナルリサーチ / マイクロアレイ / 臨床 / マクロアレイ

Research Abstract

Through analyzing epigenome and transcriptome in colorectal cancer (CRC) cells, we identified a number of microRNA genes which were epigenetically silenced in CRC. By analyzing colorectal premalignant lesions and early CRC tissues, we identified novel DNA methylation alterations, which could be potential biomarkers for early detection of CRCs. Moreover, we discovered a novel relationship between tumor surface microstructure, pathological findings and molecular alterations in the colorectal premalignant lesion. We carried out epigenome analysis the background gastric mucosa of primary gastric cancer (GC), and identified novel DNA methylation changes which could be novel GC risk markers. Finally, by performing epigenome analysis in primary hepatocellular carcinoma (HCC), we discovered novel DNA methylation changes, which could be novel HCC markers.

Research Products

• [Journal Article] Mesenchymal stem cells cancel azoxymethane-induced tumor initiation (2014)
  • Author(s): Nasuno M, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nakagaki S, Watanabe S, Idogawa M, Yamashita K, Naishiro Y, Adachi Y, Suzuki H, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: Stem Cells Volume: 32 Issue: 4 Pages: 913-925
  • DOI: 10.1002/stem.1594
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk (2014)
  • Author(s): Suzuki R, Yamamoto E, Nojima M, Maruyama R, Yamano HO, Yoshikawa K, Kimura T, Harada T, Ashida M, Niinuma T, Sato A, Nosho K, Yamamoto H, Kai M, Sugai T, Imai K, Suzuki H, Shinomura Y
  • Journal Title: J Gastroenterol Volume: ([Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors (2014)
  • Author(s): Watanabe S, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nasuno M, Yamashita K, Idogawa M, Naishiro Y, Murata M, Adachi Y, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: J Gastroenterol Volume: 49 Issue: 2 Pages: 270-282
  • DOI: 10.1007/s00535-013-0901-3
  • Peer Reviewed
• [Journal Article] The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma (2014)
  • Author(s): Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y
  • Journal Title: Tumour Biol Volume: 35 Issue: 2 Pages: 973-985
  • DOI: 10.1007/s13277-013-1131-2
  • Peer Reviewed
• [Journal Article] Methylation of a panel of microRNA genes is a novel biomarker for detection of bladder cancer (2013)
  • Author(s): Shimizu T, Suzuki H, Nojima M, Kitamura H, Yamamoto E, Maruyama R, Ashida M, Hatahira T, Kai M, Masumori N, Tokino T, Imai K, Tsukamoto T, Toyota M
  • Journal Title: Eur Urol Volume: 63 Issue: 6 Pages: 1091-1100
  • DOI: 10.1016/j.eururo.2012.11.030
  • Peer Reviewed
• [Journal Article] Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization. (2013)
  • Author(s): Sawada T, Yamamoto E, Suzuki H
  • Journal Title: Genes Chromosomes Cancer Volume: 52(2) Issue: 2 Pages: 140-9
  • DOI: 10.1002/gcc.22013
  • Peer Reviewed
• [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] Characteristics of Japanese inflammatory bowel disease susceptibility loci (2013)
  • Author(s): Arimura Y, Isshiki H, Onodera K, Nagaishi K, Yamashita K, Sonoda T, Matsumoto T, Takahashi A, Takazoe M, Yamazaki K, Kubo M, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: J Gastroenterol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk. (2013)
  • Author(s): Suzuki R, Yamamoto E, Nojima M, Maruyama R, Yamano HO, Yoshikawa K, Kimura T, Harada T, Ashida M, Niinuma T, Sato A, Nosho K, Yamamoto H, Kai M, Sugai T, Imai K, Suzuki H, Shinomura Y.
  • Journal Title: J Gastroenterol Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Characteristics of Japanese inflammatory bowel disease susceptibility loci. (2013)
  • Author(s): Arimura Y, Isshiki H, Onodera K, Nagaishi K, Yamashita K, Sonoda T, Matsumoto T, Takahashi A, Takazoe M, Yamazaki K, Kubo M, Fujimiya M, Imai K, Shinomura Y.
  • Journal Title: J Gastroenterol Volume: Epub ahead of print
  • 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] A novel pit pattern identifies the precursor of colorectal cancer derived from sessile serrated adenoma. (2012)
  • Author(s): Kimura T, Yamamoto E, Yamano HO.
  • Journal Title: Am J Gastroenterol. Volume: 107(3) Issue: 3 Pages: 460-9
  • DOI: 10.1038/ajg.2011.457
  • 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 Issue: 2 Pages: 277-85
  • DOI: 10.1007/s13277-011-0308-9
  • 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] Molecular Dissection of Premalignant Colorectal Lesions Reveals Early Onset of the CpG Island Methylator Phenotype. (2012)
  • Author(s): Yamamoto E, Suzuki H, Yamano HO
  • Journal Title: Am J Pathol Volume: 181(5) Issue: 5 Pages: 1847-61
  • DOI: 10.1016/j.ajpath.2012.08.007
  • 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 Issue: 11 Pages: 1907-1912
  • DOI: 10.1111/j.1349-7006.2012.02384.x
  • 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 Issue: 5 Pages: 1307-1317
  • DOI: 10.1007/s13277-012-0378-3
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor receptor expression is associated with aggressive phenotypes and has therapeutic activity in biliary tract cancers. (2012)
  • Author(s): Ohashi H
  • Journal Title: Cancer Sci Volume: 103 Issue: 2 Pages: 252-261
  • DOI: 10.1111/j.1349-7006.2011.02138.x
  • Peer Reviewed
• [Journal Article] Silencing of the Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer (2012)
  • Author(s): Taniguchi H, Jacinto F.V., Villanueva A, Fernandez AF, Yamamoto H, Carmona F.J, Puertas S, Marquez VE, Shinomura Y, Imai K, and Esteller M
  • Journal Title: Oncogene Volume: 31 Issue: 15 Pages: 1988-1994
  • DOI: 10.1038/onc.2011.387
  • Peer Reviewed
• [Journal Article] Possible involvement of Wnt11 in colorectal cancer progression (2011)
  • Author(s): ishioka M, Ueno K, Hazama S, et al
  • Journal Title: Mol Carcinog Volume: 10 Issue: 3 Pages: 207-217
  • DOI: 10.1002/mc.21845
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer (2011)
  • Author(s): Suzuki H
  • Journal Title: Cancer Res Volume: 71 Issue: 17 Pages: 5646-5658
  • DOI: 10.1158/0008-5472.can-11-1076
  • Peer Reviewed
• [Journal Article] Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors (2011)
  • Author(s): Seiko Kamimae
  • Journal Title: Cancer prevention research Volume: 4 Issue: 5 Pages: 674-83
  • DOI: 10.1158/1940-6207.capr-10-0214
  • 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 Issue: 15 Pages: 5048-5059
  • DOI: 10.1158/1078-0432.ccr-10-3131
  • 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
• [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., et al
  • Journal Title: PLoS One Volume: 6 Issue: 5 Pages: e19618-e19618
  • DOI: 10.1371/journal.pone.0019618
  • 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
• [Journal Article] A DNA methylation fingerprint of 1628 human samples (2011)
  • Author(s): Fernandez AF, Assenov Y, Martin-Subero JI, Balint B, Siebert R, Taniguchi H, Yamamoto H, Hidalgo M, Tan AC, Galm O, Ferrer I, Sanchez-Cespedes M, Villanueva A, Carmona J, Sanchez-Mut JV, Berdasco M, Moreno V, Capella G, Monk D, Ballestar E, Ropero S, Martinez R, Sanchez-Carbayo M, Prosper F, Agirre X, Fraga MF, Grana O, Perez-Jurado L, Mora J, Puig S, Prat J, Badimon L, Puca AA, Meltzer SJ, Lengauer T, Bridgewater J, Bock C, Esteller M
  • Journal Title: Genome Res Volume: 22(2) Issue: 2 Pages: 407-19
  • DOI: 10.1101/gr.119867.110
  • 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
  • Journal Title: Int J Oncol Volume: 39(3) Pages: 593-599
  • DOI: 10.3892/ijo.2011.1048
  • Peer Reviewed
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得とその臨床応用 (2013)
  • Author(s): 谷口博昭、山本博幸、伊東文生、今井浩三
  • Organizer: 第33回日本分子腫瘍マーカー研究会
  • Place of Presentation: 横浜市
  • Year and Date: 2013-10-02
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得 (2013)
  • Author(s): 谷口博昭、山本博幸、越川直彦、清木元治、今井浩三
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: 松本市
  • Year and Date: 2013-07-11
• [Presentation] マイクロRNA 遺伝子のエピジェネティクス異常と臨床応用 (2013)
  • Author(s): 鈴木拓,山本英一郎,丸山玲緒,鈴木 亮,清水崇,原田拓,山野泰穂,野島正寛,高塚伸太朗,新沼猛、甲斐正広,篠村恭久,今井浩三
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
• [Presentation] マイクロRNA遺伝子のエピジェネティクス異常と臨床応用 (2013)
  • Author(s): 鈴木 拓、丸山玲緒、鈴木 亮、清水 崇、原田 拓、山野泰穂、野島正寛、高塚伸太朗、新沼 猛、甲斐正広、篠村恭久、今井浩三
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得 (2013)
  • Author(s): 谷口博昭、山本博幸、今井浩三
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得とその臨床応用 (2013)
  • Author(s): 谷口博昭、山本博幸、伊東文生、今井浩三
  • Organizer: 第33回日本分子腫瘍マーカー研究会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得 (2013)
  • Author(s): 谷口博昭、山本博幸、越川直彦、清木元治、今井浩三
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: ホテルブエナビスタ松本
• [Presentation] ヒストンメチル化酵素分子の発現亢進による乳癌細胞の悪性形質獲得 (2012)
  • Author(s): 谷口博昭,山本博幸,今井浩三
  • Organizer: 72回日本癌学会学術総会
  • Place of Presentation: 横浜市
• [Remarks] 東京大学医科学研究所附属病院 抗体・ワクチンセンター
  • URL: http://www.nctimsut.org/
• [Remarks] 東京大学医科学研究所附属病院 抗体・ワクチンセンター
  • URL: http://www.nctimsut.org/