Novel treatment targeting CDKN2A gene deletion in malignant meningioma

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18389
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Osaka University
• Principal Investigator: Achiha Takamune 大阪大学, 大学院医学系研究科, 招へい教員 (00771908)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 悪性髄膜腫 / CDKN2A / TERT / 分子標的治療

Outline of Final Research Achievements

Abnormalities in the TERT and CDKN2A genes, which were newly included in the diagnostic criteria for malignant meningiomas in the WHO Classification 2021, are reported to be strongly involved in the recurrence of malignant meningiomas. We conducted an abnormality/expression analysis of TERT and CDKN2A-related genes using clinical meningioma samples from our facility, and showed that cases with TERT-p mutations and TERT gene expression have an intractable clinical course. No correlation was found between the expression of CDKN2A-related genes (p16INKa, p14ARF, CDK4/6, and MDM2) and meningioma recurrence. We analyzed the CDKN2A point mutation p.Ala148Thr, which has been reported to be involved in relapse, but no mutations were observed in our cohort.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

本研究により悪性髄膜腫におけるTERTおよびCDKN2A関連遺伝子の異常/発現について新たな知見を得ることができた。TERTおよびCDKN2A遺伝子の異常は研究期間中にWHO分類2021に新たに取り込まれ、悪性髄膜腫におけるkey oncogenic geneと考えられている。未だに有効な化学療法や放射線治療が存在しない悪性髄膜腫において今後治療標的としての研究が益々活発化すると考えられる。得られた知見を活用し、悪性髄膜腫において新規分子標的治療を確立するための更なる研究が必要である。