Genomic characterization of meningiomas.

Meningiomas are common tumours arising from the arachnoidal cap cells of the lep- tomeninges that can cause significant morbidity by compressing and potentially invading the ad- jacent brain, vasculature, and cranial nerves. Those tumours arising from the skull base and tumours with more aggressive histopathologic features (World Health Organization grades II and III) are particularly challenging to treat, fre- quently recurring even after optimal surgical re- section and growing despite radiation treat- ments. Currently, no effective chemotherapeutic options are available for recurrent and aggres- sive meningiomas. Until recently, the only ge- netic driver of meningiomas to be identified was bi-allelic loss of the tumour suppressor gene NF2 on chromosome 22, encoding the protein Merlin. However, several recent efforts have uncovered new driver mutations, particularly in the approxi- mately 40-60 % of tumours that are wild-type for NF2. Such mutations, including those in sig- nalling molecule genes such as AKT1 and SMO, epigenetic modifier genes such as KDM5C and SMARCB1, and additional genes whose function remains unclear, such as TRAF7 and KLF4, pre- dominate in grade-I tumours of the skull base. Patients with these difficult-to-treat tumours may therefore benefit from specific targeted me- dical therapies based on the mutations present in their individual tumours. Higher-grade tu- mours are characterized by increased genomic instability, particularly elevated numbers of chro- mosomal and arm-level losses, though few spe- cific genes involved in their pathogenesis have been identified apart from NF2. Here, we review these recent advances in our understanding of meningiomagenesis through genetic profiling and the potential clinical applications of these findings. Eur Assoc NeuroOncol Mag 2013; 3 (3): 102-4.