| Project/Area Number |
18K07193
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
Niimi Atsuko 藤田医科大学, 医学部, 准教授 (50508984)
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| Co-Investigator(Kenkyū-buntansha) |
梶野 泰祐 愛知県がんセンター(研究所), 分子診断TR分野, 主任研究員 (50723673)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | EGFR / ゲノム不安定化 / DNA修復 / POLD4 / DNA損傷 / DSB修復 |
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| Outline of Final Research Achievements |
POLD4, a factor in DNA replication/repair pathway, is required for the suppression of genomic instability, but the function is largely unknown. We defined POLD4-correlated genes as “POLD4 module” to elucidate the mechanism of EGFR mutation in lung adenocarcinoma. Interestingly, EGFR mutation in patient is negatively correlated with the activity of POLD4 module. RNA-seq datasets analysis showed that EGFR-specific type mutation (delins: complex mutation with deletion and insertion) are frequently observed in low POLD4 module activity group. By using human lung cancer cell lines, we found that the activity of POLD4 module highly correlated with cancer cell survival against cisplatin, which suggest that POLD4 module has a role in DNA repair.
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| Academic Significance and Societal Importance of the Research Achievements |
EGFRは肺腺がんの代表的なドライバー遺伝子であり、その変異発生のメカニズムを明らかにすることで肺腺がん発生の機序を解明できる可能性がある。本研究の結果より、POLD4モジュールの概念を取り入れることでEGFR変異特異的な変異が起きやすい核内環境について新たな情報を得ることができた。また、低POLD4モジュール活性細胞ではシスプラチン感受性が高いことが明らかとなり、将来的にはPOLD4モジュール活性の測定によりプラチナ製剤の感受性予測が可能となる可能性が示唆された。
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