Molecular and translational advances in meningiomas

Abstract

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

Fig. 1

Summary of established epigenomic and genomic landscape of sporadic meningiomas. DNA methylation profiling distinguishes 2 distinct tumor subgroups with distinct risk profiles that refine risk of recurrence beyond standard-of-care histopathological grading and are associated with typical known mutations.

Fig. 2

Sample integrated molecular-histopathological report. These reports can be used to facilitate communication of impactful histological (WHO grade, number of mitoses, specific histologies, and criteria) and key molecular findings (DNA methylation class, clinically relevant CNAs, and mutations).