Molecular genetics of meningiomas

Comprehensive genomic studies of meningioma have offered important insights about the molecular mechanisms underlying this common brain tumor. The use of next-generation sequencing techniques has identified driver mutations in approximately 80% of benign sporadic lesions, as well as epigenetic, regulatory, and copy number events that are associated with formation and disease progression. The events described to date fall into five mutually exclusive molecular subgroups that correlate with tumor location and embryological origin. Importantly, these subgroups also carry implications for clinical management, as they are predictive of histologic subtype and the likelihood of progression. Further work is necessary to understand the molecular mechanisms by which identified mutations drive tumorigenesis as well as the genomic pathways that transform benign lesions into malignancies. Progress made during the past decade has opened the door to potential molecular therapies as well as integration of meningioma genotyping data into clinical management decisions. Several pharmacologic trials are currently underway that leverage recent genomic findings to target established oncogenic pathways in refractory tumors. With the combined efforts of physicians and basic science investigators, the clinical management of meningioma will continue to make important strides in the coming years.