A clinically applicable integrative molecular classification of meningiomas

Farshad Nassiri, Jeff Liu, Vikas Patil, Yasin Mamatjan, Justin Z. Wang, Rupert Hugh-White, Andrew M. Macklin, Shahbaz Khan, Olivia Singh, Shirin Karimi, Rosario I. Corona, Lydia Y. Liu, Caroline Y. Chen, Ankur Chakravarthy, Qingxia Wei, Bharati Mehani, Suganth Suppiah, Andrew Gao, Adriana M. Workewych, Ghazaleh Tabatabai, Paul C. Boutros, Gary D. Bader, Daniel D. Carvalho, Thomas Kislinger, Kenneth Aldape and Gelareh Zadeh ()
Additional contact information
Farshad Nassiri: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Jeff Liu: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Vikas Patil: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Yasin Mamatjan: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Justin Z. Wang: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Rupert Hugh-White: University of California, Los Angeles
Andrew M. Macklin: University Health Network
Shahbaz Khan: University Health Network
Olivia Singh: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Shirin Karimi: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Rosario I. Corona: University of California, Los Angeles
Lydia Y. Liu: University of California, Los Angeles
Caroline Y. Chen: University of California, Los Angeles
Ankur Chakravarthy: University Health Network
Qingxia Wei: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Bharati Mehani: National Cancer Institute
Suganth Suppiah: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Andrew Gao: University Health Network
Adriana M. Workewych: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Ghazaleh Tabatabai: The International Consortium on Meningiomas
Paul C. Boutros: The International Consortium on Meningiomas
Gary D. Bader: University of Toronto
Daniel D. Carvalho: University Health Network
Thomas Kislinger: The International Consortium on Meningiomas
Kenneth Aldape: Princess Margaret Cancer Centre, University Health Network and University of Toronto
Gelareh Zadeh: Princess Margaret Cancer Centre, University Health Network and University of Toronto

Nature, 2021, vol. 597, issue 7874, 119-125

Abstract: Abstract Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified.

Date: 2021
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DOI: 10.1038/s41586-021-03850-3

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