Advances in meningioma genetics: novel therapeutic opportunities

Key Points Meningiomas are the most common primary intracranial tumours found in adults Meningiomas can have an aggressive course characterized by local progression and, infrequently, metastasis to other organs, even when treated with surgery and radiotherapy Key genetic and epigenetic alterations have been identified in meningiomas that strongly associate with clinicopathologic features, such as localization and prognosis, and could represent targets for drug treatment Prospective clinical trials are evaluating novel drugs on the basis of advances in the understanding of the pathobiology of treatment-resistant meningiomas In the past few years, novel insights into the links between the molecular and clinicopathological features of meningiomas have provided new opportunities for treatment options. Here, Matthias Preusser and colleagues discuss current progress and future prospects in the development of molecularly driven diagnosis and therapy for meningiomas. Meningiomas currently are among the most frequent intracranial tumours. Although the majority of meningiomas can be cured by surgical resection, ∼20% of patients have an aggressive clinical course with tumour recurrence or progressive disease, resulting in substantial morbidity and increased mortality of affected patients. During the past 3 years, exciting new data have been published that provide insights into the molecular background of meningiomas and link sites of tumour development with characteristic histopathological and molecular features, opening a new road to novel and promising treatment options for aggressive meningiomas. A growing number of the newly discovered recurrent mutations have been linked to a particular clinicopathological phenotype. Moreover, the updated WHO classification of brain tumours published in 2016 has incorporated some of these molecular findings, setting the stage for the improvement of future therapeutic efforts through the integration of essential molecular findings. Finally, an additional potential classification of meningiomas based on methylation profiling has been launched, which provides clues in the assessment of individual risk of meningioma recurrence. All of these developments are creating new prospects for effective molecularly driven diagnosis and therapy of meningiomas.