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Epigenetic dysregulation during development of HCC

Research Project

Project/Area Number 23790775
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

NAGAE Genta  東京大学, 先端科学技術研究センター, 助教 (10587348)

Research Collaborator MIDORIKAWA Yutaka  日本大学, 医学部附属病院消化器外科, 助教 (10292905)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords肝臓学 / 肝臓癌 / エピジェネティクス / 肝癌 / メチル化
Research Abstract

To investigate the molecular changes during hepatocarcinogenesis, we performed integrative genomic and epigenomic analysis of HCC progressing in a nodule-in-nodule fashion. Whereas most aberrant DNA methylation was detected already in outer nodules, additional chromosomal changes were newly observed during the progression from outer nodules to inner nodules. Some HCC show methylation-dominant changes during progression conversely. These results may suggest stepwise accumulation of both genomic and epigenomic alteration in malignant progression of HCC.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (37 results)

All 2013 2012 2011 Other

All Journal Article (19 results) (of which Peer Reviewed: 9 results) Presentation (15 results) (of which Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells2013

    • Author(s)
      Takase O, Yoshikawa M, Idei M, Hirahashi J, Fujita T, Takato T, Isagawa T, Nagae G, Suemori H, Aburatani H, Hishikawa K
    • Journal Title

      PLoS One

      Volume: 8(2) Issue: 2 Pages: e56399-e56399

    • DOI

      10.1371/journal.pone.0056399

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples.2012

    • Author(s)
      Kumano K, Arai S, Hosoi M, Taoka K,Takayama N, Otsu M, Nagae G, Ueda K,Nakazaki K, Kamikubo Y, Eto K,Aburatani H, Nakauchi H, Kurokawa M.
    • Journal Title

      Blood.

      Volume: 119(26) Pages: 6234-42

    • Related Report
      2012 Final Research Report
  • [Journal Article] Loss of5-hydroxymethylcytosine is accompanied with malignant cellular transformation.2012

    • Author(s)
      Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, Nagae G, Yoshida H, Aburatani H, Koike K.
    • Journal Title

      Cancer Sci.

      Volume: 103(4) Pages: 670-6

    • Related Report
      2012 Final Research Report
  • [Journal Article] Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency.2012

    • Author(s)
      Wang L, Tsutsumi S, Kawaguchi T, Nagasaki K, Tatsuno K, Yamamoto S, Sang F, Sonoda K, Sugawara M, Saiura A, Hirono S, Yamaue H, Miki Y, Isomura M, Totoki Y, Nagae G, Isagawa T, Ueda H, Murayama-Hosokawa S, Shibata T, Sakamoto H, Kanai Y, Kaneda A, Noda T, Aburatani H.
    • Journal Title

      Genome Res.

      Volume: 22(2) Pages: 208-19

    • Related Report
      2012 Final Research Report
  • [Journal Article] 【次世代シークエンサー 目的 別アドバンストメソッド】(第 5 章)エピジェ ネティクス解析編 ChIP-seq 解析2012

    • Author(s)
      永江玄太
    • Journal Title

      細胞工学(0287-3796)別冊次世代シークエンサー目的別アドバンストメソッド

      Pages: 150-157

    • Related Report
      2012 Final Research Report
  • [Journal Article] Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia2012

    • Author(s)
      Keiki Kumano
    • Journal Title

      BLOOD

      Volume: 119 Issue: 26 Pages: 6234-6242

    • DOI

      10.1182/blood-2011-07-367441

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation2012

    • Author(s)
      Kudo Y, Aburatani H, et al.
    • Journal Title

      Cancer Science

      Volume: 103 Issue: 4 Pages: 670

    • DOI

      10.1111/j.1349-7006.2012.02213.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency2012

    • Author(s)
      Wang L, Tsutsumi S, Kawaguchi T,Nagasaki K, Tatsuno K, Yamamoto S, SangF, Sonoda K, Sugawara M, Saiura A,Hirono S, Yamaue H, Miki Y, Isomura M,Totoki Y, Nagae G, Isagawa T, Ueda H,Murayama-Hosokawa S, Shibata T,Sakamoto H, Kanai Y, Kaneda A, Noda T,Aburatani H
    • Journal Title

      Genome Research

      Volume: 22(2) Issue: 2 Pages: 208-19

    • DOI

      10.1101/gr.123109.111

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence.2011

    • Author(s)
      Kaneda A, Fujita T, Anai M, Yamamoto S, Nagae G, Morikawa M, Tsuji S, Oshima M, Miyazono K, Aburatani H.
    • Journal Title

      PLoS Genet.

      Volume: 7(11)

    • Related Report
      2012 Final Research Report
  • [Journal Article] DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.2011

    • Author(s)
      Isagawa T, Nagae G, Shiraki N, Fujita T, Sato N, Ishikawa S, Kume S, Aburatani H.
    • Journal Title

      PLoS One.

      Volume: 6(10)

    • Related Report
      2012 Final Research Report
  • [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(23) Pages: 7187-97

    • Related Report
      2012 Final Research Report
  • [Journal Article] Methylation screening of reciprocal genome-wide UPDs identifies novel human-specific imprinted genes.2011

    • Author(s)
      Nakabayashi K, Trujillo AM, Tayama C, Camprubi C, Yoshida W, Lapunzina P, Sanchez A, Soejima H, Aburatani H, Nagae G, Ogata T, Hata K, Monk D.
    • Journal Title

      Hum Mol Genet.

      Volume: 20(16) Pages: 3188-97

    • Related Report
      2012 Final Research Report
  • [Journal Article] Tissue-specific demethylation in CpG-poor promoters during cellular differentiation.2011

    • Author(s)
      Nagae G, Isagawa T, Shiraki N, Fujita T, Yamamoto S, Tsutsumi S, Nonaka A, Yoshiba S, Matsusaka K, Midorikawa Y, Ishikawa S, Soejima H, Fukayama M, Suemori H, Nakatsuji N, Kume S, Aburatani H.
    • Journal Title

      Hum Mol Genet.

      Volume: 20(14) Pages: 2710-21

    • Related Report
      2012 Final Research Report
  • [Journal Article] 肝細胞癌の遺伝的基盤肝細胞癌の統合的 ゲノム解析の現況2011

    • Author(s)
      永江玄太
    • Journal Title

      The Liver Cancer Journal(1883-9347)

      Volume: 3巻1号 Pages: 34-39

    • Related Report
      2012 Final Research Report
  • [Journal Article] Tissue-specific demethylation in CpG-poor promoters during cellular differentiation2011

    • Author(s)
      Nagae G, Isagawa T, Shiraki N, Fujita T, Yamamoto S, Tsutsumi S, Nonaka A,Yoshiba S, Matsusaka K, Midorikawa Y,Ishikawa S, Soejima H, Fukayama M,Suemori H, Nakatsuji N, Kume S,Aburatani H
    • Journal Title

      Hum Mol Genetics

      Volume: 20(14) Issue: 14 Pages: 2710-21

    • DOI

      10.1093/hmg/ddr170

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes2011

    • 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 Research

      Volume: 71(23) Pages: 7187-97

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers2011

    • Author(s)
      Isagawa T, Nagae G, Shiraki N, Fujita T, Sato N, Ishikawa S, Kume S, Aburatani H
    • Journal Title

      PLoS ONE

      Volume: 6(10) Issue: 10 Pages: e26052-e26052

    • DOI

      10.1371/journal.pone.0026052

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Methylation screening of reciprocal genome-wide UPDs identifies novel human-specific imprinted genes2011

    • Author(s)
      Nakabayashi K, Aburatani H, et al.
    • Journal Title

      Hum Mol Genet

      Volume: 20 Issue: 16 Pages: 3188-97

    • DOI

      10.1093/hmg/ddr224

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence2011

    • Author(s)
      Kaneda A, Fujita T, Anai M, Yamamoto S,Nagae G, Morikawa M, Tsuji S, Oshima M,Miyazono K, Aburatani H
    • Journal Title

      PLoS Genetics

      Volume: 7 Issue: 11 Pages: e1002359-e1002359

    • DOI

      10.1371/journal.pgen.1002359

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞分化過程におけるシトシン 修飾のダイナミクス2012

    • Author(s)
      永江玄太
    • Organizer
      ADVANS 研究会 2012
    • Place of Presentation
      東京
    • Year and Date
      2012-12-15
    • Related Report
      2012 Final Research Report
  • [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma,2012

    • Author(s)
      Nagae G, Midorikawa Y, Tatsuno K, TsujiS, Yamamoto S, Tsutsumi S, Ishikawa S,Aburatani H
    • Organizer
      The 71th Japan Cancer Association Annual Meeting (InternationalSession)
    • Place of Presentation
      Sapporo.
    • Year and Date
      2012-09-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Epigenetics2012

    • Author(s)
      Nagae G, Shiraki N, Kamio A, Fujita T,Kume S, Aburatani H.
    • Organizer
      Cytosine methylation dynamics during hepatic differentiation Cold Spring Harbor Laboratory Meeting
    • Place of Presentation
      Cold Spring Harbor, NY(USA).
    • Year and Date
      2012-09-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma2012

    • Author(s)
      Nagae G, Midorikawa Y, Tatsuno K, Tsuji S, Yamamoto S, Tsutsumi S, Ishikawa S, Aburatani H
    • Organizer
      第6回日本エピジェネティクス研究会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-12
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 組織分化過程における低 CpG プロモーターの脱メチル化2011

    • Author(s)
      永江玄太、砂河孝行、白木伸明、末盛博文、粂昭苑、油谷浩幸
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma2011

    • Author(s)
      Nagae G, Midorikawa Y, Tatsuno K, Tsuji S, Yamamoto S, Tsutsumi S, Ishikawa S, Aburatani H
    • Organizer
      The 70th Japan Cancer Association Annual Meeting (International Session)
    • Place of Presentation
      Nagoya.
    • Year and Date
      2011-10-04
    • Related Report
      2012 Final Research Report
  • [Presentation] High-resolution profiling of DNA methylation changes during in vitro cellular differentiation2011

    • Author(s)
      Nagae G, Isagawa T, Shiraki N, Suemori H, Kume S, Aburatani H
    • Organizer
      The 9th International Workshop on Advanced Genomics
    • Place of Presentation
      Tokyo.
    • Year and Date
      2011-07-12
    • Related Report
      2012 Final Research Report
  • [Presentation] 組織分化過程における低 CpG プロモーターの脱メチル化2011

    • Author(s)
      永江玄太、砂河孝行、白木伸明、末盛博文、粂昭苑、油谷浩幸
    • Organizer
      第5回日本 エピジェネティクス研究会
    • Place of Presentation
      熊本
    • Year and Date
      2011-05-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Tissue-type specific hypomethylation in CpG-poor promoters during cellular differentiation2011

    • Author(s)
      Nagae G, Isagawa T, Shiraki N, Suemori H, Kume S, Aburatani H
    • Organizer
      The 6th Asian Epigenomics Meeting
    • Place of Presentation
      Kumamoto
    • Year and Date
      2011-05-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Tissue-type specific hypomethylation in CpG-poor promoters during cellular differentiation2011

    • Author(s)
      Nagae G, Isagawa T, Shiraki N, Suemori H, Kume S, Aburatani H
    • Organizer
      The 6th Asian Epigenomics Meeting(招待講演)
    • Place of Presentation
      熊本
    • Related Report
      2011 Research-status Report
  • [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2011

    • Author(s)
      永江玄太, 緑川泰, 辰野健二, 辻真吾, 山本尚吾, 堤修一, 石川俊平, 油谷浩幸
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] 組織分化過程における低CpGプロモーターの脱メチル化2011

    • Author(s)
      永江玄太、砂河孝行、白木伸明、末盛博文、粂昭苑、油谷浩幸
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma

    • Author(s)
      Nagae G, Midorikawa Y, Tatsuno K, Tsuji S, Yamamoto S, Tsutsumi S, Ishikawa S, Aburatani H
    • Organizer
      The 71th Japan Cancer Association Annual Meeting (International Session)
    • Place of Presentation
      Sapporo
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cytosine methylation dynamics during hepatic differentiation

    • Author(s)
      Nagae G, Shiraki N, Kamio A, Fujita T, Kume S, Aburatani H
    • Organizer
      Cold Spring Harbor Laboratory Meeting, Epigenetics
    • Place of Presentation
      Cold Spring Harbor (USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 細胞分化過程におけるシトシン修飾のダイナミクス

    • Author(s)
      永江玄太
    • Organizer
      ADVANS研究会2012
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] 細胞工学別冊 次世代シークエンサー 目的別アドバンストメソッド2012

    • Author(s)
      永江玄太
    • Total Pages
      8
    • Publisher
      学研メディカル秀潤社
    • Related Report
      2012 Annual Research Report
  • [Remarks] 東京大学先端科学技術研究センターゲノムサイエンス分野

    • URL

      http://www.genome.rcast.u-tokyo.ac.jp/

    • Related Report
      2012 Final Research Report
  • [Remarks] 東京大学先端科学技術研究センター ゲノムサイエンス分野

    • URL

      http://www.genome.rcast.u-tokyo.ac.jp/

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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