Glioma liquid biopsy of serum and cerebrospinal fluid using digital PCR and next-generation sequencer
Project/Area Number |
17K10874
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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 |
Research Field |
Neurosurgery
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Research Institution | Kyorin University |
Principal Investigator |
Saito Kuniaki 杏林大学, 医学部, 学内講師 (50446564)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | liquid biopsy / グリオーマ / digital PCR / cancer panel / glioma / 次世代シークエンサー / リキッドバイオプシー |
Outline of Final Research Achievements |
The aim of this research is to develop liquid biopsy for glioma using high-sensitive digital PCR. We extracted cell free DNA (cfDNA) from serum and cerebrospinal fluid and analyzed mutation and DNA methylation to achieve less-invasive diagnosis, early detection of recurrence and identification of biomarker. IDH1 mutation and TERT promoter mutation was identified with high sensitivity and specificity from cfDNA of glioma cases. Next generation sequencer (NGS) analysis of tumor DNA identified hypermutator phenotype and temporal heterogeneity of the glioma. Higher quality of tumor-derived circulating DNA was needed for liquid biopsy using NGS.
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Academic Significance and Societal Importance of the Research Achievements |
血清/髄液中のcfDNAを高感度解析することで、IDH変異やTERT変異などグリオーマの基本的な変異を検出することが高い感度特異度でできるようになった。グリオーマの非侵襲的な診断法の確立につながり、治療効果の判定や再発の検出としても画像診断より高い精度で行える可能性が示された。腫瘍の経時的な変化に伴う治療方針の最適化を行うことも可能となり、治療困難なグリオーマの予後改善に大きく貢献しうる。さらに、次世代シークエンサーを用いて経時的に解析が可能となれば、腫瘍の時間的多様性の解明から再発/悪性転化の機序の解明につながる可能性も秘めている。
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Report
(5 results)
Research Products
(14 results)
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[Presentation] Temozolomide-induced mismatch repair insufficiency and hypermethylation of MGMT promoter with hypermutation in malignant glioma2017
Author(s)
Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Daisuke Shimada, Satosi Kume, Shohei Iijima, Tomohiro Chiba, Junji Shibahara, Yoshiaki Shiokawa, Motoo Nagane
Organizer
22nd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
Related Report
Int'l Joint Research
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[Presentation] Integrated molecular analysis of newly diagnosed and recurrent glioblastoma after temozolomide treatment2017
Author(s)
Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Daisuke Shimada, Satosi Kume, Shohei Iijima, Tomohiro Chiba, Junji Shibahara, Yoshiaki Shiokawa, Motoo Nagane
Organizer
第35回日本脳腫瘍学会学術集会
Related Report