Elucidation of space-time in-tumor heterogeneity in lung cancer with Driver gene mutation
| Project/Area Number |
15K19941
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory surgery
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| Research Institution | Oita University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 非小細胞肺癌 / 上皮成長因子受容体 / tumor evolution / 腫瘍内不均一性 / 次世代シーケンス / 免疫染色 / RT-PCR / コピー数変異 / 免疫組織化学染色 / 免疫チェックポイント阻害剤 / PD-L1 / APOBEC |
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| Outline of Final Research Achievements |
Resected primary lung cancers harboring EGFR L858R were performed using an L858R mutant-specific antibody and scored by staining intensity (0-3) and proportion. Among 20 cases, 3 showed heterogeneous staining. For these cases, the nucleic acids were extracted from each differently stained lesion, and targeted sequencing was performed. Single nucleotide variations (SNVs) and copy number variations (CNVs) were then analyzed. Genetic analyses revealed an increase in the copy number of EGFR and CCNE1 in the IHC-positive part compared to the negative part in one case (case 1), and an increase in the copy number of EGFR and MDM2 was observed in the IHC-positive part compared to the negative part in another case (case 2). An increase in the ki-67 labeling index in the L858R-positive part in case 1 and increased apoptosis in the L858R-positive part in case 2 were observed, suggesting the functional significance of CNV changes.
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Report
(4 results)
Research Products
(17 results)
