Elucidation of malignant transformation mechanism in IDH-wildtype glioma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16823
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Akita University
• Principal Investigator: Ono Takahiro 秋田大学, 医学系研究科, 講師 (80620690)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: IDH-wild-type glioma / PI3K/MAPK pathway / EGFR amplification / TERT promoter mutation / Gain of chromosome 7 / Loss of chromosome 10

Outline of Final Research Achievements

IDH-wildtype (IDHwt) gliomas are the most common intramedullary tumors and are classificated into glioblastoma (GBM) according to the current WHO classification. On the other hand, clinically, there are cases with indolent clinical course. In this study, we compared the molecular pathological findings of IDHwt indolent diffuse glioma and typical GBM to explore the clitical factors for malignant transformation. We found that the indolent type tumors lacked the molecular features of GBM, except for MAPK pathway alterations. Such differences were associated with the glioma malignant transformation.

Free Research Field

脳腫瘍病理

Academic Significance and Societal Importance of the Research Achievements

IDH-wildtype gliomaではMAPK経路、TP53経路、RB経路の活性化のほか、EGFR増幅、TERTプロモーター変異、Chr.7+/10-といった様々な遺伝子異常が報告されている。一方、生物学的に、これらの遺伝子異常が同時多発的に生じるとは考えにくい。
本研究の結果において、IDHwt gliomaは少なくともMAPK経路の活性化単独では悪性化せず、その他のがん化経路の活性化や遺伝子異常との併存によって、悪性化を来すものと考えられた。本腫瘍群の悪性化の機序を解明するうえで、重要な結果であると言える。