2020 Fiscal Year Final Research Report
High sensitive and comprehensive liquid biopsy by digital NGS
| Project/Area Number |
18K07999
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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 53010:Gastroenterology-related
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| Research Institution | University of Yamanashi |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | リキッドバイオプシー / 分子バーコード / 次世代シークエンス / 膵癌 / 遺伝子解析 |
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| Outline of Final Research Achievements |
We assessed the utility of precise tag sequencing that eliminates PCR and sequence error-derived noises. Digital PCR was conducted for 45 patients with KRAS mutation in the EUS-FNA samples. Tag sequence of cfDNA was performed for patients with >2% allele frequency in KRAS by digital PCR. Tag sequence could detect mutations in KRAS (44%) and TP53 (28%) as well as copy number alterations in CCND2 (1 case), FGFR1 (1 case), and MYC (2 cases). Tag sequence for cfDNA and EUS-FNA samples was possible and could be informative for the clinical implication and therapeutic decisions. These results would lead to further development toward the improvement of prognosis of pancreatic cancer.
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| Free Research Field |
消化器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
採血検体から組織と同じ変異が高率に検出可能であった。実際の臨床検体を用いて、単一遺伝子のみならず網羅的な遺伝子解析が可能であったことを確認できた点が有意義である。さらに、変異DNA量が少ない検体で次世代シークエンスを行う場合、配列の読み間違い、ノイズが発生するが、分子バーコードを使用することでそれを大幅に軽減できたことを確認した点、および治療標的となりうる遺伝子異常が検出可能であった点、変異遺伝子の割合を追うことで、治療のモニタリングが可能であることを示せた点で、将来への臨床応用の可能性が近付いた。
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