• PereiraBenedito Jamilson AraújoBJA1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil., Marcondes LerarioAntonioA2Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan., Paula Rodrigues Sola, Talita de Sousa Laurentino, Dipika R Mohan, Antonio Nogueira de Almeida, Pires de AguiarPaulo HenriquePH5Medical Research ABC Medical School, Santo André, Brazil.6Pontifice Catholic University of São Paulo, Sorocaba, Brazil; and., da Silva PaivaWellingsonW4Neurosurgery Division, Department of Neurology, University of São Paulo, São Paulo, Brazil., Alda Wakamatsu, Manoel Jacobsen Teixeira, Sueli Mieko Oba-Shinjo, and MarieSuely Kazue NagahashiSKN1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil..
• 1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil.
• J. Neurosurg. 2023 Mar 1; 138 (3): 649662649-662.

ObjectiveThe authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcriptome, and protein expressions.MethodsThe authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequencing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity. The transcriptomic profile was analyzed by QuantSeq 3' mRNA-Seq. The differentially expressed genes of interest were validated at the protein level analysis by immunohistochemistry.ResultsThe transcriptomic analysis identified an upregulated set of genes related to metabolism and cell cycle and downregulated genes related to immune response and extracellular matrix remodeling in grade 2 (atypical) meningiomas, with a significant difference in recurrent compared with nonrecurrent cases. EZH2 nuclear positivity associated with grade 2, particularly with recurrent tumors and EZH2 gene expression level, correlated positively with the expression of genes related to cell cycle and negatively to genes related to immune response and regulation of cell motility.ConclusionsThe authors identified modules of dysregulated genes in grade 2 meningiomas related to the activation of oxidative metabolism, cell division, cell motility due to extracellular remodeling, and immune evasion that were predictive of survival and exhibited significant correlations with EZH2 expression.

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