Brain Invasion and Trends in Molecular Research on Meningioma

Abstract

Meningiomas are the most common primary brain tumors in adults. The treatment of non-benign me- ningiomas remains a challenging task, and after the publication of the 2021 World Health Organization classification, the importance of molecular biological classification is emerging. In this article, we intro- duce the mechanisms of brain invasion in atypical meningioma and review the genetic factors involved along with epigenetic regulation. First, it is important to understand the three major steps for brain in- vasion of meningeal cells: 1) degradation of extracellular matrix by proteases, 2) promotion of tumor cell migration to resident cells by adhesion molecules, and 3) neovascularization and supporting cells by growth factors. Second, the genomic landscape of meningiomas should be analyzed by major cat- egories, such as germline mutations in NF2 and somatic mutations in non-NF2 genes (TRAF7, KLF4, AKT1, SMO, and POLR2A). Finally, epigenetic alterations in meningiomas are being studied, with a fo- cus on DNA methylation, histone modification, and RNA interference. Increasing knowledge of the molecular landscape of meningiomas has allowed the identification of prognostic and predictive mark- ers that can guide therapeutic decision-making processes and the timing of follow-up.