Genomic Characterization of Meningiomas

European Association of NeuroOncology Magazine 2013; 3 (3): 102-104

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Keywords: AKT1,  genomic,  meningioma,  SMO

Meningiomas are common tumours arising from the arachnoidal cap cells of the leptomeninges that can cause significant morbidity by compressing and potentially invading the adjacent 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, frequently recurring even after optimal surgical resection and growing despite radiation treatments. Currently, no effective chemotherapeutic options are available for recurrent and aggressive meningiomas. Until recently, the only genetic 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 approximately 40–60 % of tumours that are wild-type for NF2. Such mutations, including those in signalling 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, predominate in grade-I tumours of the skull base. Patients with these difficult-to-treat tumours may therefore benefit from specific targeted medical therapies based on the mutations present in their individual tumours. Higher-grade tumours are characterized by increased genomic instability, particularly elevated numbers of chromosomal and arm-level losses, though few specific 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