Advances in Molecular Biological and Translational Studies in World Health Organization Grades 2 and 3 Meningiomas: A Literature Review.

The treatment of World Health Organization (WHO) grades 2 and 3 meningiomas remains difficult and controversial. The pathogenesis of high-grade meningiomas was expected to be elucidated to improve treatment strategies. The molecular biology of meningiomas has been clarified in recent years. High-grade meningiomas have been linked to NF2 mutations and 22q deletion. CDKN2A/B homozygous deletion and TERT promoter mutations are independent prognostic factors for WHO grade 3 meningiomas. In addition to 22q loss, 1p, 14p, and 9q loss have been linked to high-grade meningiomas. Meningiomas enriched in copy number alterations may be biologically invasive. Furthermore, several new comprehensive classifications of meningiomas have been proposed based on these molecular biological features, including DNA methylation status. The new classifications may have implications for treatment strategies for refractory aggressive meningiomas because they provide a more accurate prognosis compared to the conventional WHO classification. Although several systemic therapies, including molecular targeted therapies, may be effective in treating refractory aggressive meningiomas, these drugs are being tested. Systemic drug therapy for meningioma is expected to be developed in the future. Thus, this review aims to discuss the distinct genomic alterations observed in WHO grade 2 and 3 meningiomas, as well as their diagnostic and therapeutic implications and systemic drug therapies for high-grade meningiomas.