Identification of gastric cancer driver mutations by using PDX model
Project/Area Number |
18K07007
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49020:Human pathology-related
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Research Institution | National Cancer Center Japan |
Principal Investigator |
Takeshi Kuwata 国立研究開発法人国立がん研究センター, 東病院, 部門長 (00327321)
|
Project Period (FY) |
2018-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | 胃癌 / 遺伝子変異 / ドライバー遺伝子 / ゼノグラフト / ゲノム |
Outline of Final Research Achievements |
To identify the driver alteration in gastric cancer (GC), we compared gene alteration profiles between primary tumor (PT), patient-derived xenograft mode (PDX) and cell lines (CL). For the analyses, we used 34 GC PDX and 24 GC cell line, all established in our instituion. Gnemo profiling analyses revealed total gene mutation (single nucleotide variant [SNV] and insertion/deletion [Indel]) in 47 genes and 7 copy number alteration in 7 genes. The gene 、of which constitutive same alterations (SNV, Indel or CNV) between PT, PDX and CL were observed in all cases, include TP53, KRAS, MYC. We suppose these genes are the driver mutations in gastric cancer and could be the targets of precision oncology.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、胃癌について原発巣とヒト患者由来ゼノグラフトモデルおよび細胞株における遺伝子プロファイリングの結果比較より、ドライバー遺伝子の推定・同定が可能となることをしめすことができた。またPDX・細胞株にて新規発生した遺伝子変化についても、異なる環境に腫瘍細胞が適応するための意味のある変化、すなわち腫瘍の進展・転移に関連する遺伝子異常など、精密医療の発展にとって有用な情報となる可能性がある。
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Report
(5 results)
Research Products
(14 results)