Abstract

Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed retrospective global genetic and genomic analysis of 85 meningioma samples of various grades. Copy number alterations were assessed by 100K single-nucleotide polymorphism arrays and correlated with gene expression, proliferation indices and clinical outcome. In addition to chromosome 22q loss, which was detected in the majority of clinical samples, chromosome 6q and 14q loss was significantly more common in recurrent tumors and was associated with anaplastic histology. Five "classes" of meningiomas were detected by gene expression analysis that correlated with copy number alterations, recurrent status and malignant histology. These classes more accurately identified recurrent tumors relative to Ki-67 index and extent of surgical resection, and highlight substantial expression heterogeneity between meningiomas. These data offer the most complete description of the genomic landscape of meningiomas, and provide broad genomic information that may be used to further stratify meningioma patients into prognostic risk groups.

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