Genomic Biomarkers of Meningioma: A Focused Review

Abstract

Meningiomas represent a phenotypically and genetically diverse group of tumors which often behave in ways that are not simply explained by their pathologic grade. The genetic landscape of meningiomas has become a target of investigation as tumor genomics have been found to impact tumor location, recurrence risk, and malignant potential. Additionally, targeted therapies are being developed that in the future may provide patients with personalized chemotherapy based on the genetic aberrations within their tumor. This review focuses on the most common genetic mutations found in meningiomas of all grades, with an emphasis on the impact on tumor location and clinically relevant tumor characteristics. NF-2 and the non-NF-2 family of genetic mutations are summarized in the context of low-grade and high-grade tumors, followed by a comprehensive discussion regarding the genetic and embryologic basis for meningioma location and phenotypic heterogeneity. Finally, targeted therapies based on tumor genomics currently in use and under investigation are reviewed and future avenues for research are suggested. The field of meningioma genomics has broad implications on the way meningiomas will be treated in the future, and is gradually shifting the way clinicians approach this diverse group of tumors.

M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway

“…As one of the most common primary tumors of the central nervous system, meningiomas arise from the arachnoid tissue surrounding the brain [ 1 , 2 ]. Meningiomas can be defined as grade I (benign meningioma), grade II (atypical meningioma), and grade III (malignant meningioma) based on the grading criteria of the World Health Organization (WHO) [ 3 ]. The histopathological features of most meningiomas are benign (grade I), and patients with these meningiomas usually have an ideal prognosis with surgery [ 4 ].…”

Molecular determinants of outcomes in meningiomas

“…BAP1 mutant meningiomas localize to cerebral convexities, while SMO mutant meningiomas are located in the anterior skull base, but not midline. Posterior fossa meningiomas harbor mutations in NF-2, POLR2A, or AKT1E17K (43).…”

Clinical Management of Supratentorial Non-Skull Base Meningiomas

“…Deletion of NF2 activates phosphoinositide 3-kinase (PI3K), Notch, AKT, Ras/mitogen activated protein kinase, mammalian target of rapamycin (mTOR), and Hippo signaling pathways thereby enhancing cellular proliferation and tumorigenesis [ 89 , 93 , 95 ]. Overall, NF2 alterations are present in 70–80% of grade 2–3 meningiomas and 40% of grade 1 meningiomas [ 90 , 96 , 97 ]. Likewise, supratentorial NSBMs are NF2 -altered more often than skull base meningiomas [ 27 , 91 , 98 , 99 ].…”