Host and cancer genome analysis to understand lung adeno-carcinogenesis
| Project/Area Number |
17H04298
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
KONO TAKASHI 国立研究開発法人国立がん研究センター, 研究所, 分野長 (80280783)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | がん / 遺伝子 / 治療標的 / 発がん / 肺がん / ゲノム / 癌 / トランスレーショナルリサーチ / 遺伝学 / 病理学 |
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| Outline of Final Research Achievements |
Comparative genome analysis between early-stage and late stage lung cancers made us realize the following things. 1) Mutational signatures predominant in the early-stage lung cancers are not smoking related; DNA adduct formation by unspecified factors other than smoking drive mutagenesis in tumor initiation. 2) Early-stage lung cancer have frequent driver oncogene mutations, such as EGFR mutations, but infrequent TP53 and chromatin regulating gene mutations; Tumor initiation has occurred, but, these tumors have not yet genetically acquired progressive properties, such as tumor invasiveness, genome instability and tolerance to oncogene stress.
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| Academic Significance and Societal Importance of the Research Achievements |
早期肺がんの発生や原因となる変異形成の基盤となるゲノム変化の機序が明らかにされた。肺がんの予防に関しては、非喫煙者の変異シグネチャーの基盤となるDNAアダクト形成の解明とその防御が必要であること、肺がんの治療に関しては、TP53遺伝子やクロマチン制御遺伝子の異常が引き起こす悪性化機序のさらなる理解と、ドライバーがん遺伝子はもちろんのこと、クロマチン制御遺伝子の異常に対する分子標的治療法開発の重要性が一層浮き彫りにされた。これらは、難治がんである肺がんの克服に大きな指標となる基盤データであり、新たな学問や産業の活性化につながるものである。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Emergence and targeting of acquired and hereditary resistance to multikinase RET inhibition in RET-altered cancer patients2019
Author(s)
Wirth LJ, Kohno T (co-first author), Udagawa H, Ishii G, Ebata KB, Tuch B, Zhu EY, Nguyen M, Smith S, Hanson LM, Burkhard MR, Cable L, Blake JF, Condroski KR, Brandhuber BJ, Andrews S, Rothenberg SM, Goto K.
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Journal Title
JCO Prec Oncol
Volume: 3
Issue: 3
Pages: 1-7
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Evaluation and application of RNA-Seq by MinION.2019
Author(s)
Seki M, Katsumata E, Suzuki A, Sereewattanawoot S, Sakamoto Y, Mizushima-Sugano J, Sugano S, Kohno T, Frith MC, Tsuchihara K, Suzuki Y.
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Journal Title
DNA research
Volume: 26
Issue: 1
Pages: 55-65
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Targeting the Vulnerability of Glutathione Metabolism in ARID1A-Deficient Cancers.2019
Author(s)
Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H, Watanabe R, Maruyama A, Makinoshima H, Chiwaki F, Sasaki H, Kato T, Okamoto A, Kohno T.
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Journal Title
Cancer Cell
Volume: 35
Issue: 2
Pages: 177-190
DOI
Related Report
Peer Reviewed / Open Access
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