Molecular genetics of meningiomas: Building the roadmap towards personalized therapy

Neurochirurgie. 2018 Mar;64(1):22-28. doi: 10.1016/j.neuchi.2014.06.007. Epub 2014 Sep 20.

Abstract

New advances have recently been made in the field of molecular genetics and mouse modeling of meningiomas, opening new perspectives for future treatments. Recent genome-wide genotyping and exome sequencing studies have confirmed the pivotal role of NF2 in meningioma tumorigenesis, concerning roughly half of the tumors, and unraveled new mutations in non-NF2 meningiomas concerning AKT1, SMO, KLF4 and TRAF7. The molecular mechanisms underlying tumorigenesis of high histological grades have been progressively deciphered with the recent discovery of TERT promoter mutations in progressing tumors. A better understanding of the genetics and clinical behavior of high-grade meningiomas is mandatory in order to better design future clinical trials. New genetically engineered mouse models of benign and histologically aggressive meningioma represent a substantial resource for the establishment of relevant pre-clinical trials. By studying the mechanisms underlying these new tumorigenesis pathways and the corresponding mouse models, we should be able to offer personalized chemotherapy to patients with surgery- and radiation-refractory meningiomas in the near future.

Keywords: AKT1; Meningioma; Modèle souris; Mouse model; Méningiome; NF2; Proteus syndrome; SMO; Syndrome de Protée; TERT.

Publication types

  • Review

MeSH terms

  • Animals
  • Genes, Neurofibromatosis 2*
  • Genotype
  • Humans
  • Kruppel-Like Factor 4
  • Meningeal Neoplasms / genetics*
  • Meningioma / genetics*
  • Mutation
  • Precision Medicine