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 meningiomas 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 introduce 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 invasion 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 categories, 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 focus on DNA methylation, histone modification, and RNA interference. Increasing knowledge of the molecular landscape of meningiomas has allowed the identification of prognostic and predictive markers that can guide therapeutic decision-making processes and the timing of follow-up.

Keywords: Epigenomics; Genomics; Invasion; Meningioma; Translational research.

Fig. 1. Meningioma brain invasion is considered a three-step process that requires various kinds of proteases to degrade the ECM, adhesion molecules to promote tumor cell migration to resident cells, and different growth factors and neovascularization to feed and support meningioma tumor cells, leading to local brain invasion. ECM, extracellular matrix; MMPs, matrix metalloproteinases; HPSE, heparanase; HGF, hepatocyte growth factor; PDGFR, platelet-derived growth factor receptor; EGFR, endothelial growth factor receptor; VEGFR, vascular endothelial growth factor receptor. Adapted from Qin et al. Brain Tumor Pathol 2021;38:156-172, with permission of Springer Nature [8].