Integrative genome and epigenome analysis of non-coding regulatory regions in lung cancer
| Project/Area Number |
15H05576
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Tumor diagnostics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Research Collaborator |
Noguchi Masayuki
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(8 results)
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[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
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Journal Title
Science Signaling
Volume: 10
Issue: 474
Pages: 11-11
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[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.
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Journal Title
Leukemia
Volume: 32
Issue: 3
Pages: 694-702
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Genome Research
Volume: 26
Issue: 5
Pages: 612-623
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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