| Project/Area Number |
17K10784
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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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| Research Field |
Respiratory surgery
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| Research Institution | Okayama University |
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Principal Investigator |
Tomida Shuta 岡山大学, 大学病院, 准教授 (10372111)
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| Co-Investigator(Kenkyū-buntansha) |
豊岡 伸一 岡山大学, 医歯薬学総合研究科, 教授 (30397880)
宗 淳一 岡山大学, 大学病院, 講師 (90559890)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 分子バーコード / 次世代シーケンサー / 遺伝子変異解析 / 非小細胞肺癌 / EGFR / ALK / 肺癌 / co-mutation / VUS / compound mutation / 次世代シークエンサー / がんゲノム医療 / ターゲットシークエンス / 生体生命情報学 / ゲノム |
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| Outline of Final Research Achievements |
In this research, we examined the clinical usefulness of the next-generation sequencer analysis method using molecular barcode technology (molecular-barcoding NGS). After confirming the technical reproducibility of molecular-barcoding NGS, we applied it for 64 cases of lung adenocarcinoma with epithelial growth factor receptor (EGFR) mutation, and found that in 7 cases, the minor EGFR gene mutations, such as E709G/K, D761Y, G598V, and R776H, were detected.
We also applied the molecular-barcoding NGS method for a lung adenocarcinoma case with ALK fusion gene mutation, who showed resistance to the ALK inhibitor treatment. The ALK fusion gene mutation was detected in the sample obtained before treatment, and the gene mutation causing resistance to the ALK inhibitor was also detected in the sample obtained after treatment. Altogether these results showed clearly the clinical beneficial for the diagnosis of lung adenocarcinoma cases with EGFR and/or ALK mutation.
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| Academic Significance and Societal Importance of the Research Achievements |
EGFRのG719Xを有する症例で統計学的に有意に複合変異（compound mutation）が検出されることが分かった。またTCGAのPan-Lung cancerデータセットから660症例の肺腺癌症例を抽出・解析したところ、同様の傾向が確認されたことから、G719X遺伝子変異陽性の肺腺癌症例に対する診断への応用が期待される。
ALK阻害剤治療に耐性を示し、急激に増悪した症例のサンプルの解析を実施したところ、治療後のサンプルからはALK阻害剤への耐性を示すALK G1202R変異を引き起こす遺伝子変異が検出されており、ALK融合遺伝子陽性の肺腺癌症例に対する診断への応用が期待される。
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