Epigenomic analysis of gastrointestinal cancer cells

• Project/Area Number: 21790675
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: SUZUKI Hiromu Sapporo Medical University, 医学部, 助教 (20381254)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 消化器癌 / メチル化 / エピゲノム / 癌幹細胞

Research Abstract

In order to dissect the epigenome of gastrointestinal cancer, we analyzed the chromatin signatures and gene expression in colorectal cancer (CRC) cells. We carried out high-throughput ChIP-seq analysis and compared the data with gene expression and microRNA (miRNA) expression signatures. We also examined the DNA methylation and histone modifications in primary CRC tissues. Through these analyses, we identified a number of epigenetically silenced miRNA genes in CRCs. Our study provided a large set of epigenome data in CRC cells, suggesting that the data set are useful tools to identify cancer related genes or miRNAs.

Research Products

• [Journal Article] Role of DNA Methylation in the Development of Diffuse-Type Gastric Cancer. (2011)
  • Author(s): Yamamoto E, Suzuki H, Takamaru H, Yamamoto H, Toyota M, Shinomura Y.
  • Journal Title: Digestion 83 Pages: 241-249
  • Peer Reviewed
• [Journal Article] Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis. (2011)
  • Author(s): 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
  • Peer Reviewed
• [Journal Article] A Novel Correlation between LINE-1 Hypomethylation and the Malignancy of Gastrointestinal Stromal Tumors. (2010)
  • Author(s): Igarashi S, Suzuki H, Niinuma T, Shimizu H, Nojima M, Iwaki H, Nobuoka T, Nishida T, Miyazaki Y, Takamaru H, Yamamoto E, Yamamoto H, Tokino T, Hasegawa T, Hirata K, Imai K, Toyota M, Shinomura Y.
  • Journal Title: Clin Cancer Res 16 Pages: 5114-5123
  • NAID: 130004927691
  • Peer Reviewed
• [Journal Article] Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. (2010)
  • Author(s): Suzuki H, Yamamoto E, Nojima M, Kai M, Yamano HO, Yoshikawa K, Kimura T, Kudo T, Harada E, Sugai T, Takamaru H, Niinuma T, Maruyama R, Yamamoto H, Tokino T, Imai K, Toyota M, Shinomura Y.
  • Journal Title: Carcinogenesis 31 Pages: 2066-2073
  • Peer Reviewed
• [Journal Article] DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae. (2010)
  • Author(s): Awe Yamashita M, Toyota M, Suzuki H, Nojima M, Yamamoto E, Kamimae S, Watanabe Y, Kai M, Akashi H, Maruyama R, Sasaki Y, Yamano H, Sugai T, Shinomura Y, Imai K, Tokino T, Itoh F.
  • Journal Title: Cancer Sci 101 Pages: 1708-1716
  • NAID: 10026594987
  • Peer Reviewed
• [Journal Article] Array-based genomic resequencing of human leukemia. (2010)
  • Author(s): Awe Yamashita Y, Yuan J, Suetake I, Suzuki H, Ishikawa Y, Choi YL, Ueno T, Soda M, Hamada T, Haruta H, Takada S, Miyazaki Y, Kiyoi H, Ito E, Naoe T, Tomonaga M, Toyota M, Tajima S, Iwama A, Mano H.
  • Journal Title: Oncogene 29 Pages: 3723-3731
  • Peer Reviewed
• [Journal Article] Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo. (2010)
  • Author(s): MBuchert M, Athineos D, Abud HE, Burke ZD, Faux MC, Samuel MS, Jarnicki AG, Winbanks CE, Newton IP, Meniel VS, Suzuki H, Stacker SA, Nathke IS, Tosh D, Huelsken J, Clarke AR, Heath JK, Sansom OJ, Ernst M.
  • Journal Title: PLoS Genet 6
  • Peer Reviewed
• [Journal Article] IGFBP7 is a p53 Responsive Gene Specifically Silenced in Colorectal Cancer with CpG Island Methylator Phenotype. (2010)
  • Author(s): Suzuki H, Igarashi S, Nojima M, Maruyama R, Yamamoto E, Kai M, Akashi H, Watanabe Y, Yamamoto H, Sasaki Y, Itoh F, Imai K, Sugai T, Shen L, Issa JP, Shinomura Y, Tokino T, Toyota M.
  • Journal Title: Carcinogenesis 31 Pages: 342-349
  • Peer Reviewed
• [Journal Article] Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer. (2010)
  • Author(s): Fujikane T, Nishikawa N, Toyota M, Suzuki H, Nojima M, Maruyama R, Ashida M, Ohe-Toyota M, Kai M, Nishidate T, Sasaki Y, Ohmura T, Hirata K, Tokino T.
  • Journal Title: Breast Cancer Res Treat 122 Pages: 699-710
  • Peer Reviewed
• [Journal Article] Molecular analysis of single isolated glands in gastric cancers and their surrounding gastric intestinal metaplastic mucosa. (2010)
  • Author(s): Sugai T, Habano W, Jiao YF, Toyota M, Suzuki H, Tsukahara M, Koizuka H, Akasaka R, Koeda K, Wakabayashi G, Suzuki K.
  • Journal Title: Oncol Rep 23 Pages: 25-33
  • Peer Reviewed
• [Journal Article] Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. (2010)
  • Author(s): Suzuki H., et al.
  • Journal Title: Carcinogenesis Volume: 31 Pages: 2066-2073
  • Peer Reviewed
• [Journal Article] A Novel Correlation between LINE-1 Hypomethylation and the Malignancy of Gastrointestinal Stromal Tumors. (2010)
  • Author(s): Igarashi S., Suzuki H., et al.
  • Journal Title: Clinical Cancer Research Volume: 16 Pages: 5114-5123
  • NAID: 130004927691
  • Peer Reviewed
• [Journal Article] Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo. (2010)
  • Author(s): Buchert M., et al.
  • Journal Title: PLoS Genetics Volume: 6
  • Peer Reviewed
• [Journal Article] Epigenetic Profiles Distinguish Malignant Pleural Mesothelioma from Lung Adenocarcinoma. (2009)
  • Author(s): Goto Y, Shinjo K, Kondo Y, Shen L, Toyota M, Suzuki H, Gao W, An B, Fujii M, Murakami H, Osada H, Taniguchi T, Usami N, Kondo M, Hasegawa Y, Shimokata K, Matsuo K, Hida T, Fujimoto N, Kishimoto T, Issa JP, Sekido Y.
  • Journal Title: Cancer Res 69 Pages: 9073-9082
  • Peer Reviewed
• [Journal Article] Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma. (2009)
  • Author(s): Nojima M, Maruyama R, Yasui H, Suzuki H, Maruyama Y, Tarasawa I, Sasaki Y, Asaoku H, Sakai H, Hayashi T, Mori M, Imai K, Tokino T, Ishida T, Toyota M, Shinomura Y.
  • Journal Title: Clin Cancer Res 15 Pages: 4356-4364
  • Peer Reviewed
• [Journal Article] A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers : involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth. (2009)
  • Author(s): Mita H, Toyota M, Aoki F, Akashi H, Maruyama R, Sasaki Y, Suzuki H, Idogawa M, Kashima L, Yanagihara K, Fujita M, Hosokawa M, Kusano M, Sabau SV, Tatsumi H, Imai K, Shinomura Y, Tokino T.
  • Journal Title: BMC Cancer 9 Pages: 198-198
  • Peer Reviewed
• [Journal Article] Elevated Dnmt3a activity promotes polyposis in Apc Min mice by relaxing extracellular restraints on Wnt signaling. (2009)
  • Author(s): Samuel MS, Suzuki H, Buchert M, Putoczki TL, Tebbutt NC, Lundgren-May T, Christou A, Inglese M, Toyota M, Heath JK, Ward RL, Waring PM, Ernst M.
  • Journal Title: Gastroenterology 137 Pages: 902-913
  • Peer Reviewed
• [Journal Article] A Single Recombinant Adenovirus Expressing p53 and p21-targeting Artificial microRNAs Efficiently Induces Apoptosis in Human Cancer Cells. (2009)
  • Author(s): Idogawa M, Sasaki Y, Suzuki H, Mita H, Imai K, Shinomura Y, Tokino T.
  • Journal Title: Clin Cancer Res 15 Pages: 3725-3732
  • Peer Reviewed
• [Journal Article] CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB. (2009)
  • Author(s): Kashima L, Toyota M, Mita H, Suzuki H, Idogawa M, Ogi K, Sasaki Y, Tokino T.
  • Journal Title: Oncogene 28 Pages: 2643-2653
  • Peer Reviewed
• [Journal Article] Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma. (2009)
  • Author(s): Jost E, Gezer D, Wilop S, Suzuki H, Herman JG, Osieka R, Galm O.
  • Journal Title: Cancer Lett 281 Pages: 24-31
  • Peer Reviewed
• [Journal Article] IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype. (2009)
  • Author(s): Suzuki H, et al.
  • Journal Title: Carcinogenesis 31 Pages: 342-349
  • Peer Reviewed
• [Journal Article] Elevated Dnmt3a activity promotes polyposis in Apc(Min) mice by relaxing extracellular restraints on Wnt signaling. (2009)
  • Author(s): Samuel MS, et al.
  • Journal Title: Gastroenterology 137 Pages: 902-913
  • Peer Reviewed
• [Journal Article] Epigenetic profiles distinguish malignant pleural mesothelioma from lung adenocarcinoma. (2009)
  • Author(s): Goto Y, et al.
  • Journal Title: Cancer Research 69 Pages: 9073-9082
  • Peer Reviewed
• [Presentation] 大腸癌においてエピジェネティックに不活化したmicroRNAの網羅的解析 (2010)
  • Author(s): 鈴木拓
  • Organizer: 日本エピジェネティクス研究会
  • Place of Presentation: 米子市
  • Year and Date: 2010-05-28
• [Presentation] 消化管問質腫瘍におけるHNE-1低メチル化と悪性度との相関 (2010)
  • Author(s): 山本英一郎, 鈴木拓, 新沼猛, 五十嵐伸一, 山本博幸, 豊田実, 篠村恭久
  • Organizer: 第21回日本消化器癌発生学会総会
  • Place of Presentation: 軽井沢
• [Presentation] GISTにおけるエピジェネティックな異常とその臨床的意義 (2010)
  • Author(s): 鈴木拓, 新沼猛, 篠村恭久
  • Organizer: 第18回日本消化器病関連学会週間
• [Presentation] CIMP大腸癌の起源 (2010)
  • Author(s): 山本英一郎, 鈴木拓, 山野泰穂, 神前正幸, 甲斐正広, 菅井有, 時野隆至, 今井浩三, 篠村恭久, 豊田実
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 次世代シークエンサーを用いた遺伝子転写開始点予測とエピゲノム解析への応用 (2010)
  • Author(s): 泰史, 篠村恭久, 時野隆至, 今井浩三
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 大腸がん・胃がん細胞におけるDGKGのエピジェネティック制御 (2010)
  • Author(s): 甲斐正広, 鈴木拓, 山本英一郎, 今井浩三, 豊田実
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 胃癌におけるmicroRNA34b/cのエピジェネティックな不活化 (2010)
  • Author(s): 鈴木拓, 山本英一郎, 高丸博之, 五十嵐伸一, 野島正寛, 山本博幸, 豊田実, 今井浩三, 篠村恭久
  • Organizer: 第6回日本消化管学会学術集会
  • Place of Presentation: 福岡
• [Presentation] 大腸癌においてエピジェネティックに不活性したmicroRNAの網羅的解析 (2009)
  • Author(s): 鈴木拓
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] 多発胃癌背景胃粘膜における異常メチル化 (2009)
  • Author(s): 山本英一郎, 豊田実, 鈴木拓, 山本博幸, 山野泰穂, 菅井有, 今井浩三, 篠村恭久
  • Organizer: 第20回日本消化器癌発生学会総会
  • Place of Presentation: 広島
• [Presentation] 大腸癌におけるIGFBP7のメチル化とCIMPとの相関 (2009)
  • Author(s): 鈴木拓, 五十嵐伸一, 高丸博之, 新沼猛, 山本英一郎, 野島正寛, 山本博幸, 豊田実, 今井浩三, 篠村恭久
  • Organizer: 第20回日本消化器癌発生学会総会
  • Place of Presentation: 広島
• [Presentation] 大腸癌においてエピジェネティックに不活化したmicroRNAの網羅的解析 (2009)
  • Author(s): 鈴木拓, 五十嵐伸一, 高丸博之, 新沼猛, 山本博幸, 時野隆至, 今井浩三, 豊田実, 篠村恭久
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 大腸発癌におけるDNAメチル化の役割 (2009)
  • Author(s): 山本英一郎, 山野泰穂, 鈴木拓, 野島正寛, 丸山玲緒, 時野隆至, 今井浩三, 篠村恭久, 豊田実
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Book] バイサルファイトPCR法.(改訂第5版新遺伝子工学ハンドブック)(村松正實, 山本雅, 岡崎康司編) (2010)
  • Author(s): 鈴木拓, 豊田実
  • Publisher: 東京 羊土社
• [Book] 改訂第5版 新遺伝子工学ハンドブック,村松正實,山本雅,岡崎康司編 (2010)
  • Author(s): 鈴木拓
  • Publisher: 羊土社
• [Book] Inflammation and Cancer Methods and Protocols : Volume 2: Molecular Analysis and Pathways (Inflammation-related aberrant patterns of DNA methylation : detection and role in epigenetic deregulation of cancer cell transcriptome.)(Methods in Molecular Biology Edited by Serguei V.Kozlov.) (2009)
  • Author(s): Suzuki H, Toyota M, Kondo Y, Shinomura Y.
  • Total Pages: 512
  • Publisher: Humana Press, New York, USA.