Stratification of gastroenterological tumors by genome-wide analysis of DNA methylation alteration.

• Project/Area Number: 22390255
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: KANEDA Atsushi 東京大学, 先端科学技術研究センター, 特任准教授 (10313024)
• Co-Investigator(Renkei-kenkyūsha): TSUTSUMI Shuichi 東京大学, 先端科学技術研究センター, 特任准教授 (30345152) ; UOZAKI Hiroshi 東京大学, 医学部附属病院, 講師 (10296246)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2010: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 小腸大腸肛門外科学 / 癌 / エピゲノム / エピジェネティクス / マイクロアレイ / 次世代シーケンサー / 情報工学

Research Abstract

DNA methylation analysis on genome-wide scale revealed three distint epigenotypes in gastric cancer and Epstein-Barr virus infection is the cause for extensive DNA methylation epigenotype. As for colorectal cancer, DNA methylation epigenotypes was found to be established already at adenoma stage; serrated adenoma showed high-methylation epigenotype with strong correlation to BRAF mutation, while non-serrated adenoma was classified into intermediate- and low-methylation epigenotypes.

Research Products

• [Journal Article] Intermediate methylation epigenotype and its correlation to KRAS mutation in conventional colorectal adenoma (2012)
  • Author(s): Yagi K, Takahashi H, Akagi K, Matsusaka K, Seto Y, Aburatani H, Nakajima A,Kaneda A
  • Journal Title: Am J Pathology Volume: 180(2) Issue: 2 Pages: 616-25
  • DOI: 10.1016/j.ajpath.2011.10.010
  • Peer Reviewed
• [Journal Article] Epstein-Barr virusinfection as an epigenetic driver of tumorigenesis (2012)
  • Author(s): Kaneda A, Matsusaka K, Aburatani H, Fukayama M
  • Journal Title: Cancer Research Volume: Vol.72 Issue: 14 Pages: 3445-3450
  • DOI: 10.1158/0008-5472.can-11-3919
  • Peer Reviewed
• [Journal Article] がんエピゲノムマーカー (2012)
  • Author(s): 金田篤志
  • Journal Title: 日本臨床 Volume: 70 Pages: 749-753
• [Journal Article] がんエビゲノムマーカー (2012)
  • Author(s): 金田篤志
  • Journal Title: 日本臨床 Volume: (In press)(掲載確定)
• [Journal Article] Two groups of DNA methylation markers to classify colorectal cancer into three epigenotypes (2011)
  • Author(s): Kaneda, A., and Yagi, K
  • Journal Title: Cancer Sci Volume: 102 Pages: 18-24
  • NAID: 10029288084
• [Journal Article] Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes (2011)
  • Author(s): Matsusaka K, Kaneda A, Nagae G, Ushiku T, Kikuchi Y, Hino R, Uozaki H, Seto Y,Takada K, Aburatani H, Fukayama M
  • Journal Title: Cancer Res Volume: 71 Issue: 23 Pages: 7187
  • DOI: 10.1158/0008-5472.can-11-1349
  • Peer Reviewed
• [Journal Article] HCCとエビゲノム (2011)
  • Author(s): 金田篤志
  • Journal Title: 肝胆膵 Volume: 62 Pages: 933-943
• [Journal Article] がんのエビゲノム異常 (2011)
  • Author(s): 金田篤志
  • Journal Title: 細胞 Volume: 43 Pages: 504-507
• [Journal Article] Two groups of DNA methylation markers to classify colorectal cancer into three epigenotypes. (2011)
  • Author(s): Kaneda A, Yagi K
  • Journal Title: Cancer Sci Volume: 102 Pages: 18-24
  • NAID: 10029288084
  • Peer Reviewed
• [Journal Article] HCCとエピゲノム (2011)
  • Author(s): 金田篤志
  • Journal Title: 肝胆膵 Volume: 62(In press掲載確定)
• [Journal Article] Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma (2010)
  • Author(s): Deng, Y.B., Nagae, G., Midorikawa, Y., Yagi, K., Tsutsumi, S., Yamamoto, S., Hasegawa, K., Kokudo, N., Aburatani, H., and Kaneda, A
  • Journal Title: Cancer Sci Volume: 101 Pages: 1501-1510
  • NAID: 10026593919
• [Journal Article] Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma. (2010)
  • Author(s): Deng YB, Kaneda A, et al.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1501-1510
  • NAID: 10026593919
  • Peer Reviewed
• [Journal Article] DNAメチローム解析技術の発展と最新テクノロジー (2010)
  • Author(s): 金田篤志
  • Journal Title: 実験医学 Volume: 28 Pages: 1765-1773
• [Journal Article] 癌診断とエピゲノム (2010)
  • Author(s): 金田篤志
  • Journal Title: 医学のあゆみ Volume: 235 Pages: 1038-1044
• [Presentation] Accumulation of epigenetic alteration involved in gastrointestinal carcinogenesis (2013)
  • Author(s): Atsushi Kaneda
  • Organizer: 2nd Joint Global COE Symposium of The IMSUT & RCAST Global COE, The University of Tokyo and Chiba University Global COE "Current and Future Trends in Genome-based Immunity, Infection and Cance
  • Place of Presentation: 東京
  • Year and Date: 2013-01-28
• [Presentation] Infection of Epstein-Barr virus is epigenetic driver of tumorigenesis (2012)
  • Author(s): Atsushi Kaneda
  • Organizer: 2nd Japanese-French Cancer Workshop
  • Place of Presentation: 徳島
  • Year and Date: 2012-11-30
• [Presentation] 胃癌におけるDNA超高メチル化群とEBウィルス感染 (2012)
  • Author(s): 金田篤志ら
  • Organizer: 第23回日本消化器
  • Place of Presentation: 徳島
  • Year and Date: 2012-11-16
• [Presentation] 大腸癌における3群のエピジェノタイプと予後 (2012)
  • Author(s): 金田篤志
  • Organizer: 日本消化器関連学会週間(JDDW)
  • Place of Presentation: 神戸
  • Year and Date: 2012-10-11
• [Presentation] エピゲノム異常と大腸癌発生 (2012)
  • Author(s): 金田篤志
  • Organizer: 岩手県大腸癌病理研究会
  • Place of Presentation: 盛岡
  • Year and Date: 2012-06-15
• [Presentation] PRC2 overexpression and H3K27me3 modification in small cell lung cancer (2011)
  • Author(s): Teruyuki Sato, Atsushi Kaneda, et al.
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Markedly high methylation epigenotype identified in EB virus(+) gastric cancer and its induction by EB virus infection (2011)
  • Author(s): Keisuke Matsusaka, Atsushi Kaneda
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Decoding the genome and transcriptome of human pancreatic cancer by integrated next-generation sequencing technologies (2011)
  • Author(s): Linghua Wang, Atsushi Kaneda, et al.
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Development of DNA methylation epigenotypes and their correlation to oncogene mutation in colorectal adenoma (2011)
  • Author(s): Koichi Yagi, Atsushi Kaneda, et al.
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Epigenomic profiling of oral cancer (2011)
  • Author(s): Sayaka Yoshiba, Atsushi Kaneda, et al.
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 大腸癌前癌病変におけるDNAメチル化エピジェノタイプ (2011)
  • Author(s): 八木浩一、金田篤志, ら
  • Organizer: 第5回日本エピジェネティクス研究会年会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-19
• [Presentation] 甲状腺乳頭癌、濾胞癌におけるエピジェネティック変異に関する検討 (2011)
  • Author(s): 菊池弥寿子、金田篤志, ら
  • Organizer: 第5回日本エピジェネティクス研究会年会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-19
• [Presentation] DNA Methylation Profiling of Papillary and Follicular Thyroid Cancer (2011)
  • Author(s): Yasuko Kikuchi, Atsushi Kaneda, et al.
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] The role of inflammatory genes in cellular senescence (2010)
  • Author(s): Katayama Y, Kaneda A, et al.
  • Organizer: 第33回分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 癌遺伝子変異と相関するエピジェノタイプと、癌遺伝子変異による早期細胞老化における重要因子のゲノム探索 (2010)
  • Author(s): 金田篤志, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大坂
  • Year and Date: 2010-09-24
• [Presentation] ゲノムワイドなプロモーターメチル化解析による肝癌の分子生物学的層別化 (2010)
  • Author(s): 永江玄太、金田篤志, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大坂
  • Year and Date: 2010-09-24
• [Presentation] 口腔癌におけるエピゲノム解析 (2010)
  • Author(s): 葭葉清香、金田篤志, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大坂
  • Year and Date: 2010-09-23
• [Presentation] 甲状腺腫瘍におけるDNAメチル化のプロファイリングおよび遺伝子変化について (2010)
  • Author(s): 菊池弥寿子、金田篤志, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大坂
  • Year and Date: 2010-09-23
• [Presentation] 肺小細胞癌株のヒストン修飾異常に関する検討 (2010)
  • Author(s): 佐藤輝幸、金田篤志, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大坂
  • Year and Date: 2010-09-23
• [Presentation] 定量的メチル化解析による大腸癌・腺腫のエピジェノタイピング (2010)
  • Author(s): 八木浩一、金田篤志ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] 定量的メチル化解析による大腸癌・腺腫のエピジェノタイピング (2010)
  • Author(s): 八木浩一、金田篤志, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大坂
  • Year and Date: 2010-09-22
• [Presentation] EBV関連胃癌におけるDNAメチル化の網羅的解析 (2010)
  • Author(s): 松坂恵介、金田篤志, ら
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大坂
  • Year and Date: 2010-09-22
• [Presentation] Three epigenotypes of colorectal cancer revealed by epigenotyping through quantitative DNA methylation analysis (2010)
  • Author(s): Kaneda A
  • Organizer: The 3rd World Cancer Congress 2010
  • Place of Presentation: Singapore, Republic of Singapore
  • Year and Date: 2010-06-23
• [Presentation] Three epigenotypes of colorectal cancer revealed by epigenotyping through quantitative DNA methylation analysis (2010)
  • Author(s): Kaneda A
  • Organizer: The 3^<rd> World Cancer Congress 2010
  • Place of Presentation: Singapore, Republic of Singapore
  • Year and Date: 2010-06-23
• [Presentation] DNAメチル化情報を用いた大腸癌の3つのエピジェノタイプの同定 (2010)
  • Author(s): 八木浩一、金田篤志, ら
  • Organizer: 第4回日本エピジェネティクス研究会年会
  • Place of Presentation: 米子
  • Year and Date: 2010-05-29
• [Presentation] 甲状腺乳頭癌におけるDNAメチル化解析
  • Author(s): 菊池弥寿子、金田篤志ら
  • Organizer: 第６回日本エピジェネティクス研究会年会
  • Place of Presentation: 東京
• [Presentation] DNA methylation alteration of Epstein-Barr virus genome and host cellular genome in EBV infection into gastric cels
  • Author(s): Keisuke Matsusaka, Atsushi Kaneda, et al.
  • Organizer: 第７１回日本癌学会総会
  • Place of Presentation: 札幌
• [Presentation] DNA methylation Analysis of Papillary Thyroid Cancer
  • Author(s): Yasuko Kikuchi, Atsushi Kaneda, et al.
  • Organizer: 第７１回日本癌学会総会
  • Place of Presentation: 札幌
• [Presentation] Analysis of histone modification alteration in gastric cancer cells during Epstein-Barr virus infection
  • Author(s): Sayaka Funata, Atsushi Kaneda, et al.
  • Organizer: 第７１回日本癌学会総会
  • Place of Presentation: 札幌
• [Presentation] 大腸癌における３群のエピジェノタイプと予後.
  • Author(s): 金田篤志
  • Organizer: 日本消化器関連学会週間(JDDW).
  • Place of Presentation: 神戸
  • Invited
• [Presentation] 胃癌におけるDNA超高メチル化群とEBウィルス感染.
  • Author(s): 金田篤志ら
  • Organizer: 第23回日本消化器癌発生学会総会シンポジウム
  • Place of Presentation: 徳島
• [Presentation] Infection of Epstein-Barr virus is epigenetic driver of tumorigenesis.
  • Author(s): Atsushi Kaneda
  • Organizer: 2nd Japanese-French Cancer Workshop
  • Place of Presentation: 徳島
• [Presentation] Accumulation of epigenetic alteration involved in gastrointestinal carcinogenesis.
  • Author(s): Atsushi Kaneda
  • Organizer: 2nd Joint Global COE Symposium of The IMSUT & RCAST Global COE, The University of Tokyo and Chiba University Global COE “Current and Future Trends in Genome-based Immunity, Infection and Cancer”
  • Place of Presentation: 東京
  • Invited
• [Book] In "Epigenomics From Chromatin Biology to Therapeutics" (2012)
  • Author(s): Kaneda A
• [Book] Cancer classification by genome-wide and quantitative DNA methylation analyses. In "Epigenomics From Chromatin Biology to Therapeutics"(Krishnarao Appasani Ed.) (2012)
  • Author(s): Kaneda A
  • Publisher: Cambridge University Press
• [Remarks]
  • URL: http://www.genome.rcast.u-tokyo.ac.jp/
• [Remarks]
  • URL: http://www.genome.rcast.u-tokyo.ac.jp/
• [Remarks]
  • URL: http://www.genome.reast.u-tokyo.ac.jp/
• [Patent(Industrial Property Rights)] 癌細胞の存否を判定する方法および癌患者の予後を判定する方法 (2010)
  • Inventor(s): 金田篤志ら
  • Industrial Property Rights Holder: 京大学など
  • Filing Date: 2010-06-30
• [Patent(Industrial Property Rights)] 特許 (2010)
  • Inventor(s): 金田篤志, ら
  • Industrial Property Rights Holder: 東京大学, など
  • Filing Date: 2010-06-30
  • Overseas
• [Patent(Industrial Property Rights)] 特許 (2010)
  • Inventor(s): 金田篤志, ら
  • Industrial Property Rights Holder: 東京大学など
  • Filing Date: 2010-06-30
  • Overseas