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Integrative genome and epigenome analysis of non-coding regulatory regions in lung cancer

Research Project

Project/Area Number 15H05576
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Tumor diagnostics
Research InstitutionUniversity of Tsukuba

Principal Investigator

Muratani Masafumi  筑波大学, 医学医療系, 教授 (50730199)

Research Collaborator Noguchi Masayuki  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2016: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywordsがんゲノム / エピゲノム / ヒストン修飾 / 非コード制御領域 / 臨床組織検体 / 肺癌 / ゲノミクス / 癌 / エンハンサー / プロモーター / 微量検体 / エピゲノム解析 / 体細胞変異 / ゲノム / 病理学 / 発現制御 / ゲノム制御
Outline of Final Research Achievements

Unlike coding mutations, extent of somatic mutations in non-coding regulatory regions remains largely unknown. In this study, we performed ChIP-sequencing analysis of lung cancer clinical tissue samples. Discovery of large number of somatic mutations in promoters and other regulatory regions indicates potential impact of non-coding mutations in cancer. ChIP-sequencing also identified allele-specific regulation of cancer-associated regulatory regions. Such information is highly useful to filter potential functional variants, and similar strategy could be applied to other clinical research including rare diseases. It is also important to develop method to utilize functional variants as diagnostic markers and as drug targets. Functional SNPs could be developed as a predictive marker for disease susceptibility, and somatic mutations could predict effect of drugs targeting certain transcriptional regulatory network.

Academic Significance and Societal Importance of the Research Achievements

既知の癌関連遺伝子の近傍のゲノム制御領域に多数の体細胞変異が見つかったことは、癌のゲノム変異解析において未知の領域があることを示しており、それらの機能的意義の確立や多数症例での研究など、今後の研究の基礎となる結果が得られた。全ゲノム解析の情報に加え、癌特異的に変化する制御領域の位置情報とアレル特異的制御の情報を加えることで、多数の変異から機能的に重要なものを効果的にフィルタリングできることは今後の癌研究にも有用である。制御領域の変異をどのように臨床応用するかは今後の課題ではあるが、SNPによる疾患感受性の予測やクリプティック・プロモーターからの転写産物に対する創薬などが期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (8 results)

All 2018 2017 2016 Other

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Genetic evidence implies that primary and relapsed tumors arise from common precursor cells in primary central nervous system lymphoma2018

    • Author(s)
      Hattori Keiichiro、Sakata-Yanagimoto Mamiko、Kusakabe Manabu、Nanmoku Toru、Suehara Yasuhito、Matsuoka Ryota、Noguchi Masayuki、Yokoyama Yasuhisa、Kato Takayasu、Kurita Naoki、Nishikii Hidekazu、Obara Naoshi、Takano Shingo、Ishikawa Eiichi、Matsumura Akira、Muratani Masafumi、Hasegawa Yuichi、Chiba Shigeru
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 1 Pages: 401-407

    • DOI

      10.1111/cas.13848

    • NAID

      120007128280

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The transcription factor MAFK induces EMT and malignant progression of triple-negative breast cancer cells through its target GPNMB2017

    • Author(s)
      Yukari Okita, Minori Kimura, Rudy Xie, Chen Chen, Larina Tzu-Wei Shen, Yurika Kojima, Hiroyuki Suzuki, Masafumi Muratani, Masao Saitoh, Kentaro Semba, Carl-Henrik Heldin, Mitsuyasu Kato
    • Journal Title

      Science Signaling

      Volume: 10 Issue: 474 Pages: 11-11

    • DOI

      10.1126/scisignal.aak9397

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma2017

    • Author(s)
      Fujisawa M., Sakata-Yanagimoto M., Nishizawa S., Komori D., Gershon P., Kiryu M., Tanzima S., Fukumoto K., Enami T., Muratani M., Yoshida K., Ogawa S., Matsue K., Nakamura N., Takeuchi K., Izutsu K., Fujimoto K., Teshima T., Miyoshi H., Gaulard P., Ohshima K., Chiba S.
    • Journal Title

      Leukemia

      Volume: 32 Issue: 3 Pages: 694-702

    • DOI

      10.1038/leu.2017.273

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.2016

    • Author(s)
      Kumar V, Rayan NA, Muratani M, Lim S, Elanggovan B, Lixia X, Lu T, Makhija H, Poschmann J, Lufkin T, Ng HH, Prabhakar S.
    • Journal Title

      Genome Research

      Volume: 26 Issue: 5 Pages: 612-623

    • DOI

      10.1101/gr.201038.115

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Integrative genome and epigenome analysis of gene regulatory regions in human lung cancer cells isolated by laser-micro-dissection2018

    • Author(s)
      Masafumi Muratani, Shingo Sakashita, Naomi Kaneko, Masayuki Noguchi
    • Organizer
      Human Genome Meeting 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] より柔軟に、より低コストでー筑波大学のNGS解析プラットフォーム2017

    • Author(s)
      村谷匡史
    • Organizer
      冬の若手ワークショップ
    • Place of Presentation
      一宮シーサイドオーツカ・千葉県・一宮町
    • Year and Date
      2017-01-30
    • Related Report
      2016 Annual Research Report
  • [Remarks] LMDを用いたゲノム・エピゲノム統合解析

    • URL

      http://www.md.tsukuba.ac.jp/tmrc/foundation_core/gb/genome-biology.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] トランスボーダー医学研究センター ゲノム生物学分野

    • URL

      http://www.md.tsukuba.ac.jp/tmrc/foundation_core/gb/genome-biology.html

    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2022-11-04  

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