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Integrated analysis of genetic and epigenetic alterations in hepatocellular carcinoma.

Research Project

Project/Area Number 26293172
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKyoto University

Principal Investigator

Marusawa Hiroyuki  京都大学, 医学(系)研究科(研究院), 准教授 (80324630)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywords肝癌 / 遺伝子変異 / AID
Outline of Final Research Achievements

Liver cancers, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma, generally arise in liver chronically inflamed due to various diseases such as hepatitis virus infection and steatohepatitis. Chronic inflammation triggers the aberrant expression of a DNA mutator enzyme, activation-induced cytidine deaminase (AID), and contributes to tumorigenesis through the accumulation of genetic aberrations. To gain further insight into the inflammation-mediated genotoxic events required for carcinogenesis, we examined the role of chronic inflammation in the emergence of genetic aberrations in the liver with constitutive AID expression. We found that inflammation-mediated transcriptional upregulation of target genes, including putative tumor suppressor genes, enhances the opportunity for inflamed cells to acquire somatic mutations and contributes to the acceleration of tumorigenesis in the inflamed liver tissues.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(19 results)

All 2016 2015 2014

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 7 results,  Open Access: 3 results) Presentation (11 results) (of which Invited: 1 results)

  • [Journal Article] MSH2 dysregulation is triggered by proinflammatory cytokine stimulation and is associated with liver cancer development.2016

    • Author(s)
      Eso Y, Takai A, Matsumoto T, Inuzuka T, Horie T, Ono K, Uemoto S, Lee K, Edelmann W, Chiba T, Marusawa H
    • Journal Title

      Cancer Research

      Volume: 76 Pages: 4383-4393

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TERT promoter mutations and chromosome 8p loss are characteristic of nonalcoholic fatty liver disease-related hepatocellular carcinoma.2016

    • Author(s)
      Ki Kim S, Ueda Y, Hatano E, Kakiuchi N, Takeda H, Goto T, Shimizu T, Yoshida K, Ikura Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Uemoto S, Chiba T, Ogawa S, Marusawa H.
    • Journal Title

      Int J Cancer

      Volume: 139 Pages: 2512-2518

    • DOI

      10.1002/ijc.30379

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hepatic inflammation facilitates transcription-associated mutagenesis via AID activity and enhances liver tumorigenesis2015

    • Author(s)
      Matsumoto T, Shimizu T, Nishijima N, Ikeda A, Eso Y, Matsumoto Y, Chiba T, Marusawa H
    • Journal Title

      Carcinogenesis

      Volume: 36 Pages: 904-913

    • DOI

      10.1093/carcin/bgv065

    • NAID

      120005676642

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations.2015

    • Author(s)
      Sawai Y, Kodama Y, Shimizu T, Ota Y, Maruno T, Eso Y, Kurita A, Shiokawa M, Tsuji Y, Uza N, Matsumoto Y, Masui T, Uemoto S, Marusawa H, Chiba T.
    • Journal Title

      Cancer Res

      Volume: 15 Pages: 32923301-32923301

    • DOI

      10.1158/0008-5472.can-14-3028

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exploring the Mechanisms of Gastrointestinal Cancer Development Using Deep Sequencing Analysis2015

    • Author(s)
      Matsumoto T, Shimizu T, Takai A, Marusawa H
    • Journal Title

      Cancers

      Volume: 7 Pages: 1037-1051

    • DOI

      10.3390/cancers7020823

    • NAID

      120005670861

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection.2014

    • Author(s)
      Shimizu T, Marusawa H, Matsumoto Y, Inuzuka T, Ikeda A, Fujii Y, Minamiguchi S, Miyamoto S, Kou T, Sakai Y, Crabtree JE, Chiba T.
    • Journal Title

      Gastroenterrology

      Volume: 147 Pages: 407-417

    • DOI

      10.1053/j.gastro.2014.04.036

    • NAID

      120005466713

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Leptin receptor somatic mutations are frequent in HCV-infected cirrhotic liver and associated with hepatocellular carcinoma.2014

    • Author(s)
      Ikeda A, Shimizu T, Matsumoto Y, Fujii Y, Eso Y, Inuzuka T, Mizuguchi A, Shimizu K, Hatano E, Uemoto S, Chiba T, Marusawa H
    • Journal Title

      Gastroenterology

      Volume: 146 Pages: 222-232

    • DOI

      10.1053/j.gastro.2013.09.025

    • NAID

      120005372982

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A model of liver carcinogenesis originating from hepatic progenitor cells with accumulation of genetic alterations.2014

    • Author(s)
      Soo Ki Kim, Akihiro Nasu, Junji Komori, Takahiro Shimizu, Yuko Matsumoto, Yasuko Minaki, Kenji Kohno, Kazuharu Shimizu, Shinji Uemoto, Tsutomu Chiba, Hiroyuki Marusawa.
    • Journal Title

      Int. J. Cancer

      Volume: 134 Pages: 1067-1076

    • DOI

      10.1002/ijc.28445

    • NAID

      120005588051

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Genomic approaches to uncover clonal structure and oncogenic potential of liver cirrhosis2016

    • Author(s)
      Kim SK, Ogawa S, Marusawa H
    • Organizer
      第58回日本消化器病学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝炎症発癌におけるDNAミスマッチ修復遺伝子MSH2の発現低下と変異パターンの関連性2016

    • Author(s)
      恵荘裕嗣、高井淳、千葉勉、妹尾浩、丸澤宏之
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] EpCAM陽性肝幹/前駆細胞は肝細胞癌の起源となる2016

    • Author(s)
      松本知訓、高井淳、恵荘裕嗣、千葉勉、妹尾浩、丸澤宏之
    • Organizer
      第75回日本癌学会学術総
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝癌の発生母地としての肝硬変組織に潜在するゲノム異常2016

    • Author(s)
      金秀基、吉田健一、垣内伸之、上田佳秀、南口早智子、海道利実、白石友一、宮野悟、羽賀博典、上本伸二、妹尾浩、小川誠司、丸澤宏之
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 消化器癌のゲノムワイドなコピー数異常と全ゲノムコピー数解析の実際2015

    • Author(s)
      丸澤宏之
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県 名古屋国際会議場
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 脂肪肝疾患に由来するヒト肝がんのゲノム異常の特性2015

    • Author(s)
      金秀基、後藤知之、千葉勉、丸澤宏之
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵癌進展におけるactivation-induced cytidine deaminase(AID)の役割2015

    • Author(s)
      大田悠司、澤井勇吾、児玉裕三、丸澤宏之、千葉勉
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 食道扁平上皮癌の染色体コピー数異常における予後関連因子の検討2015

    • Author(s)
      後藤知之、島田裕、金秀基、清水孝洋、髙井淳、千葉勉、丸澤宏之
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] NBNC肝癌におけるNASH肝癌の位置づけとゲノム異常の網羅的解析2014

    • Author(s)
      金秀基、波多野悦朗、丸澤宏之
    • Organizer
      第56回日本消化器病学会大会
    • Place of Presentation
      ポートピアホテル本館 兵庫県 神戸市
    • Year and Date
      2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 慢性炎症は転写上昇を介してゲノム変異導入を亢進し肝発癌を促進する2014

    • Author(s)
      松本知訓、西島規浩、千葉勉、丸澤宏之
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 横浜市 神奈川県
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mutation profiles of hepatocellular carcinoma developed in nonalcoholic fatty liver disease. 脂肪性肝疾患に発生する肝癌のゲノム異常解析2014

    • Author(s)
      金秀基、千葉勉、丸澤宏之
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 横浜市 神奈川県
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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