The multiomic landscape of meningiomas: a review and update

Meningiomas are the most common primary brain tumor in adults. Traditionally they have been understudied compared to other central nervous system (CNS) tumors. However over the last decade, there has been renewed interest in uncovering the molecular topography of these tumors, with landmark studies identifying key driver alterations contributing to meningioma development and progression. Recent work from several independent research groups have integrated different genomic and epigenomic platforms to develop a molecular-based classification scheme for meningiomas that could supersede histopathological grading in terms of diagnostic accuracy, biological relevance, and outcome prediction, keeping pace with contemporary grading schemes for other CNS tumors including gliomas and medulloblastomas.

Here we summarize the studies that have uncovered key alterations in meningiomas which builds towards the discovery of consensus molecular groups in meningiomas by integrating these findings. These groups supersede WHO grade and other clinical factors in being able to accurately predict tumor biology and clinical outcomes following surgery.

Despite differences in the nomenclature of recently uncovered molecular groups across different studies, the biological similarities between these groups enables us to likely reconciliate these groups into four consensus molecular groups: two benign groups largely dichotomized by NF2-status, and two clinically aggressive groups defined by their hypermetabolic transcriptome, and by their preponderance of proliferative, cell-cycling pathways respectively.

Future work, including by our group and others are underway to validate these molecular groups and harmonize the nomenclature for routine clinical use.