| Project/Area Number |
21K09136
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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 56010:Neurosurgery-related
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐々木 重嘉 杏林大学, 医学部, 助教 (20894504)
市村 幸一 順天堂大学, 医学部, 特任教授 (40231146)
永根 基雄 杏林大学, 医学部, 教授 (60327468)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 中枢神経系悪性リンパ腫 / リキッドバイオプシー / マルチプレックスqPCR / MYD88 / CD79B / CNS lymphoma / liquid biopsy |
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| Outline of Research at the Start |
中枢神経系悪性リンパ腫(CNSL)は、高齢者に特に高頻度に発生する原発性悪性脳腫瘍であり、現在の診断法である脳生検術は、耐術能の低い高齢者への侵襲や周術期合併症が課題となっている。低侵襲に診断を行うべく液性診断(liquid biopsy)への期待が高まっており、本研究では髄液中遊離DNA(cell free DNA; cfDNA)を用い、CNSLの特異的遺伝子変異であるMYD88遺伝子変異、CD79B遺伝子変異を、digital PCR法、BNA Clamp-quantitative PCR(BNA-qPCR)法により検出するCNSL診断法を前方視的に検証し、臨床応用を目指す。
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| Outline of Final Research Achievements |
Central nervous system lymphoma (CNSL) is the second most common primary malignant brain tumors in elderly. In order to avoid risk of operation in elderly patients, we developed a simple and robust liquid biopsy method utilizing a BNA Clamp-quantitative PCR(BNA-qPCR) method using cell-free DNA (cfDNA) extracted from the cerebrospinal fluid (CSF). More than 90% of CNSL harbor mutations in either MYD88 or CD79B. This method enables detection of mutations in either MYD88 or CD79B in a single multiplex qPCR assay. In a dilution experiment, our assay detected mutations of the variant allele frequency of as low as 0.5%. The consistency of the mutations between the matched tumor and cfDNA from CSF was 73.3%. We will investigate the nature of inconsistencies and further improve the sensitivity and specificity of the assay with the aim to establish a clinically applicable test.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢者のCNSL疑いの症例に、手術による生検を行うことなく本検査によって診断を確定することができれば、高齢者の手術による合併症を減らし、ADLの向上も期待できる。
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