Development of non-invasive novel diagnostic methods for primary central nervous system lymphoma using liquid biopsy for nucleic acids derived from cerebrospinal fluid

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10873
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kyorin University
• Principal Investigator: Shiokawa Yoshiaki 杏林大学, 医学部, 教授 (20245450)
• Co-Investigator(Kenkyū-buntansha): 市村 幸一 国立研究開発法人国立がん研究センター, 研究所, 分野長 (40231146)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 中枢神経系原発悪性リンパ腫 / Liquid biopsy / MYD88 / CD79B

Outline of Final Research Achievements

In this study, we aimed to establish a diagnostic method for detecting MYD88 and CD79B mutations, which are frequently mutated in PCNSL, from DNA in CSF. DNA was extracted from the CSF of 42 PCNSL cases, the optimal test conditions for the MYD88 mutation detection using digital PCR were established, and the test accuracy was verified. When the Target/Total value of 0.25% was set as the cutoff using the optimum amount of DNA yield in CSF, the sensitivity was 92.2% and the specificity was 100%, showing extremely high test accuracy. For the CD79B mutation, we are developing a diagnostic method by the qPCR.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

本研究で定めた検査条件では、髄液中DNAに対するdigital PCR法を用いたMYD88 L265P変異検出法は非常に高い検査精度であった。MYD88変異またはCD79B変異を有する症例はPCNSL全体の約9割に上り(Nakamura T, Neuropathol Appl Neurobiol 42(3): 279-90, 2016)、本検査法の確立によりPCNSL患者の大半で生検術を回避できる可能性がある。迅速かつ低侵襲な確定診断の達成により、生検術困難な患者への適切な治療介入、身体的活動度の維持、QOL向上、ひいては現病の予後改善にも寄与することが期待される。