Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel

Kenta Ohara; Satoru Miyawaki; Hirofumi Nakatomi; Atsushi Okano; Yu Teranishi; Yuki Shinya; Daiichiro Ishigami; Hiroki Hongo; Shunsaku Takayanagi; Shota Tanaka; Aya Shinozaki-Ushiku; Shinji Kohsaka; Hidenori Kage; Katsutoshi Oda; Kiyoshi Miyagawa; Hiroyuki Aburatani; Hiroyuki Mano; Kenji Tatsuno; Nobuhito Saito

doi:10.3389/fneur.2023.1270046

Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel

Front Neurol. 2023 Nov 23:14:1270046. doi: 10.3389/fneur.2023.1270046. eCollection 2023.

Authors

Kenta Ohara¹, Satoru Miyawaki¹, Hirofumi Nakatomi¹, Atsushi Okano¹, Yu Teranishi¹, Yuki Shinya¹, Daiichiro Ishigami¹, Hiroki Hongo¹, Shunsaku Takayanagi¹, Shota Tanaka¹, Aya Shinozaki-Ushiku², Shinji Kohsaka³, Hidenori Kage⁴, Katsutoshi Oda⁵, Kiyoshi Miyagawa⁶, Hiroyuki Aburatani⁷, Hiroyuki Mano³, Kenji Tatsuno⁷, Nobuhito Saito¹

Affiliations

¹ Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
² Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan.
³ Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
⁴ Department of Next-Generation Precision Medicine Development Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁵ Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁶ Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁷ Genome Science and Medicine Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.

Abstract

Background: Despite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies.

Case presentation: We report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach.

Conclusion: Gene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.

Keywords: Todai OncoPanel; actionable gene aberration; comprehensive genomic analysis; malignant meningioma; malignant progression.

Publication types

Case Reports

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We performed sequencing analysis and interpretation of the data under a grant from the Program for an Integrated Database of Clinical and Genomic Information (JP19kk0205016) from the Japan Agency for Medical Research and Development and a grant from Sysmex Corporation.