Meningioma Genomics: Diagnostic, Prognostic, and Therapeutic Applications

Abstract

There has been a recent revolution in our understanding of the genetic factors that drive meningioma, punctuating an equilibrium that has existed since Cushing's germinal studies nearly a century ago. A growing appreciation that meningiomas share similar biologic features with other malignancies has allowed extrapolation of management strategies and lessons from intra-axial central nervous system neoplasms and systemic cancers to meningiomas. These features include a natural proclivity for invasion, frequent intratumoral heterogeneity, and correlation between biologic profile and clinical behavior. Next-generation sequencing has characterized recurrent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA, which are collectively present in ~80% of sporadic meningiomas. Genomic features of meningioma further associate with tumor location, histologic subtype, and possibly clinical behavior. Such genomic decryption, along with advances in targeted pharmacotherapy, provides a maturing integrated view of meningiomas. We review recent advances in meningioma genomics and probe their potential applications in diagnostic, therapeutic, and prognostic frontiers.

Keywords: genomics; meningioma; molecular taxonomy; precision medicine; targeted therapy.

Figure 1

Demographics, WHO diagnostic criteria, histologic subtypes, and clinical outcomes at 10 years follow-up for meningioma, as stratified by grade. ^§Clinical outcomes are influenced by age, comorbidities, extent of resection, adjuvant therapy, and tumor location.

Figure 2

(A) Recurrent NF2, AKT1, SMO, TRAF7, KLF4, and PIK3CA mutations are collectively present in over 80% of grade I meningiomas. Mutations in AKT1, KLF4, and PIK3CA overlap with TRAF7, but not with each other, and largely occur in a mutually exclusive pattern with NF2 and SMO. Oncogenic driver mutations remain unclear for ~20% of meningiomas [Data aggregated from Ref. (19, 20, 23, 41)]. (B) Recurrent chromosomal copy number alterations in meningioma. Chromosomal arm-level gains (red) and losses (blue) are observed with increasing frequency in higher-grade meningiomas, compared to grade I meningiomas. ^§Polysomy 5 is observed in angiomatous subtype of grade I meningiomas [Data adapted from Ref. (5, 32)].