Analysis on tumor-immune interaction landscape in CNS germ cell tumors

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17918
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takami Hirokazu 東京大学, 医学部附属病院, 助教 (50548625)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胚細胞腫 / RNAシークエンス / メチル化解析 / コピー数異常 / 予後

Outline of Final Research Achievements

RNA sequence was performed for 58 CNS germ cell tumors (GCTs), which demonstrated germinoma and non-germinomatous GCTs (NGGCTs) were clearly distinct on transcriptome, that NGGCTs harbor immune cells including M2 macrophages, and that they were akin to testicular GCTs with regards to transcriptome and methylome. Tumor markers and histopathological entities were correlated in 162 cases. This analysis unraveld that tumor markers were unexpectedly elevated in germinomas and teratomas, which casted a cautious look on the standardized treatment decision-making based on tumor markers alone. Another important achievement was that methylation analysis in 82 CNS GCT cases demonstrated 12p gain was frequent in CNS GCTs; and 12p gain was associated with NGGCT histology, and also was correlated with worse prognosis. Finally, abundance of lymphocytes in germinoma was proved to be a good prognosis marker, which was demonstrated in histopathologica/clinical studies.

Free Research Field

腫瘍のゲノム解析

Academic Significance and Societal Importance of the Research Achievements

中枢神経胚細胞腫は東アジアに多い疾患であり、歴史的に日本が臨床研究において大きな成果を出してきた分野である。基礎研究についても過去10年において日本が主導権を握りつつあり、この科研費研究はその主導権の掌握において極めて大きい役割を果たした。具体的には中枢神経胚細胞腫の特徴的な発現様式、免疫細胞浸潤のプロファイルと予後マーカーとしての役割、そして12p増幅という新たなバイオマーカーの同定が新しい発見であった。これに続く科研費研究にて更なる発展を目指し、胚細胞腫の治療標的の同定を目標としている。