Quantification of fusion cfDNA and resistant mutation cfRNA in plasma EVs from patients with lung cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16847
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Yoshtiaka Seki 東京慈恵会医科大学, 医学部, 講師 (00733213)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 治療耐性因子探索 / 融合遺伝子陽性肺がん / cfDNA / チロシンキナーゼ阻害薬

Outline of Final Research Achievements

At first, we attempted to establish a method for quantitative detection of mutations by cfDNA and detection of fusion genes. As a result, we found that Guardant Health's commercial-based analysis method was useful for detecting fusion genes. Therefore, we decided to proceed with the estimation of resistance mechanisms from other related genes based on the company's analysis method, using a research protocol approved by the hospital research ethics review committee. A genetic search for resistance mechanisms was successfully conducted after collecting and analyzing blood samples from fusion gene-positive patients at the time of TKI resistance. As a result, he reported at the conference that candidate genes for fusion genes and resistance can be detected in blood samples, and that further analysis could lead to clinical applications.

Free Research Field

ゲノム生物学

Academic Significance and Societal Importance of the Research Achievements

fDNAによる変異の定量的検出、融合遺伝子の検出法の確立を試みた。その結果、融合遺伝子の検出についてはGuardant Health社のコマーシャルベースの解析法が有用である事が判明した。融合遺伝子陽性患者TKI耐性化時の血液サンプルを収集し解析した上で耐性機序の遺伝学的検索に成功した。融合遺伝子・耐性の候補遺伝子が血液検体から検出できること、今後のさらなる解析の積み重ねにより臨床応用も可能となりうることについて学会で報告した。