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Molecular mechanisms of aberrant DNA methylation during multistage carcinogenesis

Research Project

Project/Area Number 21790371
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionNational Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East

Principal Investigator

ARAI Eri  独立行政法人国立がん研究センター, 研究所, 研究員 (40446547)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords分子病理学 / 腫瘍 / DNAメチル化 / DNMT1 / 発がんリスク評価 / 分子病理
Research Abstract

The aim of this study is to detect the molecules which associate with DNA methyltransferase (DNMT)1 and contribute to induce aberrant DNA methylation profiles during human carcinogenesis. We used HepG2 cell line which was derived from human liver cancer and showed high expression levels of DNMT1. We performed immunoprecipitation of DNMT1 using optimum antibody in HepG2 nuclear extract, and separated immunoprecipitant by SDS-PAGE. Co-precipitated proteins were analyzed by 2 Dimensional Image Converted Analysis of LCMS (2D-ICAL method), and the candidate molecule which may associate DNMT1 and may contribute aberrant DNA methylation was identified. Direct association between the candidate molecule and DNMT1 is being evaluated. Mechanisms how the candidate molecule participates in aberrant distribution of DNMT1 resulting in aberrant DNA methylation profiles will be examined.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (55 results)

All 2011 2010 2009

All Journal Article (21 results) (of which Peer Reviewed: 8 results) Presentation (32 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Copy number alterations in urothelial carcinomas : Their clinicopathological significance and correlation with DNA methylation alterations.2011

    • Author(s)
      Nishiyama N, Arai E, Nagashio R, Fujimoto H, Hosoda F, Shibata T, Tsukamoto T, Kanai Y.
    • Journal Title

      Carcinogenesis 32

      Pages: 462-469

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genome-wide DNA methylation profiles in renal tumors of various histological subtypes and non-tumorous renal tissues.2011

    • Author(s)
      Arai E., Wakai-Ushijima S., Fujimoto H., Hosoda F., Shibata T., Kondo T., Yokoi S., Imoto I., Inazawa J., Hirohashi S., Kanai Y.
    • Journal Title

      Pathobiology 78

      Pages: 1-9

    • Related Report
      2010 Final Research Report
  • [Journal Article] Diagnosis and prognostication of ductal adenocarcinomas of the pancreas based on genome-wide DNA methylation profiling by bacterial artificial chromosome array-based methylated CpG island amplification.2011

    • Author(s)
      Gotoh M, Arai E, Wakai-Ushijima S, Hiraoka N, Kosuge T, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Kanai Y.
    • Journal Title

      J Biomed Biotech

    • Related Report
      2010 Final Research Report
  • [Journal Article] Carcinogenetic risk estimation based on quantification of DNA methylation levels in liver tissue at the precancerous stage.2011

    • Author(s)
      Nagashio R, Arai E, Ojima H, Kosuge T, Kondo Y, Kanai Y.
    • Journal Title

      Int J Cancer (in press.)

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genome-wide DNA methylation profiles in renal tumors of various histological subtypes and non-tumorous renal tissues2011

    • Author(s)
      Arai E, et al.
    • Journal Title

      Pathobiology

      Volume: 78 Pages: 1-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Copy number alterations in urothelial carcinomas : their clinicopathological significance and correlation with DNA methylation alterations.2011

    • Author(s)
      Nishiyama N, et al.
    • Journal Title

      Carcinogenesis

      Volume: 32 Pages: 462-469

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnosis and prognostication of ductal adenocarcinomas of the pancreas based on genome-wide DNA methylation profiling by bacterial artificial chromosome array-based methylated CpG island amplification.2011

    • Author(s)
      Gotoh M, et al.
    • Journal Title

      J Biomed Biotechnol

      Volume: 2011

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carcinogenetic risk estimation based on quantification of DNA methylation levels in liver tissue at the precancerous stage.2011

    • Author(s)
      Nagashio R, et al.
    • Journal Title

      Int J Cancer

      Volume: (in print)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic and epigenetic alterations during renal carcinogenesis (review).2010

    • Author(s)
      Arai E, Kanai Y.
    • Journal Title

      Int J Clin Exp Pathol 4

      Pages: 58-73

    • Related Report
      2010 Final Research Report
  • [Journal Article] DNA methylation profiles in precancerous tissue and cancers : Carcinogenetic risk estimation and prognostication based on DNA methylation status (review).2010

    • Author(s)
      Arai E, Kanai Y.
    • Journal Title

      Epigenomics 2

      Pages: 467-481

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genetic and epigenetic alterations during renal carcinogenesis.2010

    • Author(s)
      Arai E, et al.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 4 Pages: 58-73

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage2010

    • Author(s)
      Nishiyama N, et al.
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 231-240

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage2010

    • Author(s)
      Nishiyama N, et al.
    • Journal Title

      Cancer Science 101

      Pages: 231-240

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 上皮内癌2010

    • Author(s)
      新井恵吏, 他
    • Journal Title

      病理と臨床 28巻臨時増刊号

      Pages: 218-219

    • Related Report
      2009 Annual Research Report
  • [Journal Article] フィールド効果2010

    • Author(s)
      中川徹, 他
    • Journal Title

      病理と臨床 28巻臨時増刊号

      Pages: 214-215

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage.2009

    • Author(s)
      Nishiyama N, Arai E, Chihara Y, Fujimoto H, Hosoda F, Shibata T, Kondo T, Tsukamoto T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y.
    • Journal Title

      Cancer Sci 101

      Pages: 231-240

    • NAID

      10027200383

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma.2009

    • Author(s)
      Arai E, Ushijima S, Gotoh M, Ojima H, Kosuge T, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y.
    • Journal Title

      Int J Cancer 125

      Pages: 2854-2862

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome.2009

    • Author(s)
      Arai E, Ushijima S, Fujimoto H, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y.
    • Journal Title

      Carcinogenesis 30

      Pages: 214-221

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma2009

    • Author(s)
      Arai E, et al.
    • Journal Title

      International Journal of Cancer 125

      Pages: 2854-2862

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ゲノム網羅的DNAメチル化解析に基づく発がんリスク評価とがんの個性診断2009

    • Author(s)
      新井恵吏
    • Journal Title

      病理と臨床 27

      Pages: 641-647

    • Related Report
      2009 Annual Research Report
  • [Journal Article] DNAメチル化異常の分子病理診断への展開2009

    • Author(s)
      新井恵吏, 他
    • Journal Title

      医学のあゆみ 229

      Pages: 8231-8236

    • Related Report
      2009 Annual Research Report
  • [Presentation] 腎細胞がん発生過程におけるDNAメチル化異常の網羅的解析2011

    • Author(s)
      新井恵吏, 森泰昌, 知久季倫, 後藤政広, 中川徹, 藤元博行, 金井弥栄
    • Organizer
      日本エピジェネティクス研究会第5回年会
    • Place of Presentation
      熊本
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 慢性障害肝におけるDNAメチル化状態を指標とした発がんリスク評価の肝生検検体を用いた臨床応用2011

    • Author(s)
      長塩亮, 新井恵吏, 尾島英, 小菅智男, 金井弥栄
    • Organizer
      日本エピジェネティクス研究会第5回年会
    • Place of Presentation
      熊本
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 泌尿器系腫瘍及びその背景組織のメチル化解析2011

    • Author(s)
      新井恵吏, 金井弥栄
    • Organizer
      日本病理学会第100回総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 酸化ストレス誘発ラット腎癌は高度な染色体不安定性を示す2011

    • Author(s)
      赤塚慎也, 山下依子, 岡崎泰昌, 蒋麗, 永井裕崇, 新井恵吏, 金井弥栄, 豊國伸哉
    • Organizer
      日本病理学会第100回総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Copy number alterations in urothelial carcinomas : Their clinicopathological significance and correlation with DNA methylation alterations.2011

    • Author(s)
      Nishiyama N, Arai E, Nagashio R, Fujimoto H, Hosoda F, Shibata T, Tsukamoto T, Yokoi S, Imoto I, Inazawa J, Kanai Y.
    • Organizer
      AACR 102^<nd> annual meeting 2011
    • Place of Presentation
      Orlando, FL.
    • Related Report
      2010 Final Research Report
  • [Presentation]2011

    • Author(s)
      Nishiyama N, et al.
    • Organizer
      AACR 102^<nd> annual meeting 2011
    • Place of Presentation
      Orlando, FL
    • Related Report
      2010 Annual Research Report
  • [Presentation] Focal DNA methyltransferase 3B expression is associated with poor outcome of stage I testicular seminoma2010

    • Author(s)
      Arai E, et al.
    • Organizer
      Epigenetics and Stem Cells
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2010-08-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Genome-wide DNA methylation profiles in renal tumors of various histological subtypes and non-tumorous renal tissues2010

    • Author(s)
      Arai E, et al.
    • Organizer
      AACR special conference, Cancer epigenetics
    • Place of Presentation
      San Juan, Puerto Rico
    • Year and Date
      2010-01-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Stage I精巣セミノーマにおけるDNMT3B巣状発現は再発予測指標となる2010

    • Author(s)
      新井恵吏, 若井-牛島抄織, 中川徹, 藤元博行, 金井弥栄
    • Organizer
      日本癌学会第69回学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] DNAメチル化を指標とする慢性肝障害患者における発がんリスク評価法の開発2010

    • Author(s)
      長塩亮, 新井恵吏, 尾島英知, 小菅智男, 近藤豊, 金井弥栄
    • Organizer
      日本癌学会第69回学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] DNAメチル化プロファイルに基づいた膵がんの存在診断・病態診断指標の確立2010

    • Author(s)
      後藤政広, 新井恵吏, 若井-牛島抄織, 平岡伸介, 小菅智男, 細田文恵, 柴田龍弘, 近藤格, 横井左奈, 井本逸勢, 稲澤譲治, 金井弥栄
    • Organizer
      日本癌学会第69回学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Focal DNA methyltransferase 3B expression is associated with poor outcome of stage I testicular seminoma.2010

    • Author(s)
      Arai E, Ushijima-Wakai S, Nakagawa T, Fujimoto H, Kanai Y.
    • Organizer
      Epigenetics and Stem Cells Conference
    • Place of Presentation
      Copenhagen, Denmark.
    • Related Report
      2010 Final Research Report
  • [Presentation] Focal DNA methyltransferase 3B expression is associated with poor outcome of stage I testicular seminoma.2010

    • Author(s)
      新井恵吏, 若井-牛島抄織, 中川徹, 藤元博行, 金井弥栄
    • Organizer
      日本エピジェネティクス研究会第4回年会
    • Place of Presentation
      米子
    • Related Report
      2010 Final Research Report
  • [Presentation] DNAメチル化を指標とする慢性肝障害患者における発がんリスク評価法の開発2010

    • Author(s)
      長塩亮, 新井恵吏, 尾島英知, 小菅智男, 近藤豊, 金井弥栄
    • Organizer
      日本エピジェネティクス研究会第4回年会
    • Place of Presentation
      米子
    • Related Report
      2010 Final Research Report
  • [Presentation] DNAメチル化プロファイルに基づいた膵がんの存在診断・病態診断指標の確立2010

    • Author(s)
      後藤政広, 新井恵吏, 平岡伸介, 小菅智男, 細田文恵, 柴田龍弘, 近藤格, 横井左奈,井本逸勢, 稲澤譲治, 金井弥栄
    • Organizer
      日本エピジェネティクス研究会第4回年会
    • Place of Presentation
      米子
    • Related Report
      2010 Final Research Report
  • [Presentation] Genome-wide DNA methylation profiles in renal tumors of various histological subtypes and non-tumorous renal tissues.2010

    • Author(s)
      Arai E, Ushijima-Wakai S, Fujimoto H, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y.
    • Organizer
      AACR special conference, Cancer epigenetics
    • Place of Presentation
      San Juan, Puerto Rico.
    • Related Report
      2010 Final Research Report
  • [Presentation] DNAメチル化状態を指標とする慢性肝障害患者における発がんリスク評価法の開発2010

    • Author(s)
      長塩亮, 他
    • Organizer
      日本癌学会第69回学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] 精巣Stage IセミノーマにおけるDNMT3B巣状発現は腫瘍再発予測指標となる2010

    • Author(s)
      新井恵吏, 他
    • Organizer
      日本エピジェネティクス研究会第4回年会
    • Place of Presentation
      米子, 鳥取
    • Related Report
      2010 Annual Research Report
  • [Presentation] DNAメチル化プロファイルに基づいた膵がんの存在診断・病態診断指標の確立2010

    • Author(s)
      後藤政広, 他
    • Organizer
      日本エピジェネティクス研究会第4回年会
    • Place of Presentation
      米子, 鳥取
    • Related Report
      2010 Annual Research Report
  • [Presentation] DNAメチル化状態を指標とする慢性肝障害患者における発がんリスク評価法の開発2010

    • Author(s)
      長塩亮, 他
    • Organizer
      日本エピジェネティクス研究会第4回年会
    • Place of Presentation
      米子, 鳥取
    • Related Report
      2010 Annual Research Report
  • [Presentation] DNAメチル化異常を指標とした肝細胞がんのリスク評価と予後予測2009

    • Author(s)
      新井恵吏, 他
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜,神奈川
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] 尿路上皮がんならびに前がん段階にある尿路上皮におけるDNAメチル化プロファイルー発がんリスク評価と予後予測2009

    • Author(s)
      西山直隆, 他
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜,神奈川
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] 定量的DNAメチル化解析に基づく尿路上皮がん診断示標2009

    • Author(s)
      千原良友, 他
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜,神奈川
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] 鉄ニトリロ三酢酸誘発ラット腎癌に見られる高度の染色体不安定性2009

    • Author(s)
      赤塚慎也, 他
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜,神奈川
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] 種々の組織亜型の腎腫瘍におけるDNAメチル化プロファイル2009

    • Author(s)
      新井恵吏, 他
    • Organizer
      日本エピジェネティクス研究会第3回年会
    • Place of Presentation
      千代田区,東京
    • Year and Date
      2009-05-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Regional DNA hypermethylation and copy number alterations during renal carcinogenesis2009

    • Author(s)
      Arai E, et al.
    • Organizer
      AACR 100^<th> annual meeting 2009
    • Place of Presentation
      Denver,CO
    • Year and Date
      2009-04-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] DNAメチル化の変化を指標とした肝細胞がんのリスク評価と予後予測2009

    • Author(s)
      新井恵吏, 牛島抄織, 後藤政広, 尾島英知, 小菅智男, 細田文恵, 柴田龍弘, 近藤格, 横井左奈, 井本逸勢, 稲澤譲治, 廣橋説雄, 金井弥栄
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 尿路上皮がんならびに前がん状態にある尿路上皮におけるDNAメチル化プロファイル-発がんリスク評価と予後予測2009

    • Author(s)
      西山直隆, 新井恵吏, 藤元博行, 細田文恵, 柴田龍弘, 近藤格, 塚本泰司, 横井左奈, 井本逸勢, 稲澤譲治, 廣橋説雄, 金井弥栄
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 定量的DNAメチル化解析に基づく尿路上皮がん診断示標2009

    • Author(s)
      千原良友, Gangning Liang, Peter Jones, 新井恵吏, 藤元博行, 菅野康吉, 藤本清秀, 平尾佳彦, 金井弥栄
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 鉄ニトリロ三酢酸誘発ラット腎癌に見られる高度の染色体不安定性2009

    • Author(s)
      赤塚慎也, 山下依子, 蒋麗, 大原浩貴, 泉谷昌志, 阿部浩一郎, 中釜斉, 村上秀樹, 関戸好孝, 新井恵吏, 金井弥栄, 樋野興夫, 豊國伸哉
    • Organizer
      日本癌学会第68回学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 種々の組織亜型の腎腫瘍におけるDNAメチル化プロファイル2009

    • Author(s)
      新井恵吏, 牛島抄織, 藤元博行, 細田文恵, 柴田龍弘, 近藤格, 横井左奈, 井本逸勢, 稲澤譲治, 廣橋説雄, 金井弥栄
    • Organizer
      日本エピジェネティクス研究会第3回年会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Genome-wide DNA methylation alterations and copy number alterations during renal carcinogenesis.2009

    • Author(s)
      Arai E, Ushijima S, Fujimoto H, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, Kanai Y.
    • Organizer
      AACR 100th annual meeting
    • Place of Presentation
      Denver, CO.
    • Related Report
      2010 Final Research Report
  • [Book] DNA methylation status in chronic liver disease and hepatocellular carcinoma (review).(Grisham JW, Thorgeirsson S, Springer)2010

    • Author(s)
      Kanai Y, Arai E.
    • Publisher
      In : Molecular Genetics of Liver Neoplasia. ed.
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] Pyrosequencing技術を用いてDNAメチル化状態を定量評価し肝細胞がんの発生リスクを評価する方法2011

    • Inventor(s)
      金井弥栄、新井恵吏、長塩亮
    • Industrial Property Rights Holder
      金井弥栄、新井恵吏、長塩亮
    • Industrial Property Number
      2011-016695
    • Filing Date
      2011-01-28
    • Related Report
      2010 Annual Research Report 2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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