Genetic analysis of spinal cord glioma and identification of novel therapeutic targets

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10857
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: The University of Tokyo
• Principal Investigator: Tanaka Shota 東京大学, 医学部附属病院, 講師 (80643725)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: glioma / astrocytoma / ependymoma / spinal cord / genetic analysis / methylation / whole exome sequencing

Outline of Final Research Achievements

This study aimed to unveil clinical and genetic profiles of diffuse glioma and ependymoma in the spinal cord. Thirty cases of astrocytoma and 58 cases of ependymoma treated at Dokkyo Medical University, Tokyo Metropolitan Neurological Hospital, Osaka City University, or The University of Tokyo between 2000 and 2016 were included in the study. Diffuse midline glioma, H3K27M-mutant was diagnosed in 9 cases (30%). They were all high-grade with variable clinical pictures (age, location, etc). IDH1-R132S mutation was noted in 1 case. WHO grade was significantly associated with overall survival, whereas H3K27M mutation was not. Clustering of the DNA methylation data on spinal ependymoma suggested relative homogeneity among WHO grade 2 cases; however, clustering using probes of HOX cluster genes clearly differentiated them according to tumor location.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

脊髄に発生する神経膠腫（グリオーマ）は治癒困難で予後不良であり、上衣腫は概して予後良好だが再発や播種を来す症例もある。本研究にて国内屈指のコホートを構築した。稀少疾患である脊髄グリオーマ・上衣腫の臨床像を明らかにするとともに、その分子プロファイルを探索することができた。脊髄グリオーマにおいては、脳幹グリオーマとは異なり病理学的な悪性度が予後に与える影響が大きいことが示唆され、安全な限り最大の検体収集が重要と思われた。脊髄上衣腫においては、発生母地が体節分化後であることが示唆され、頭蓋内ほどの生物学的な不均一性はないものと思われた。これらの新たな知見は日常診療の一助になり得ると期待される。