GSTM1 null genotype underpins recurrence of NF2 meningiomas

Introduction: Meningiomas are the most common primary central nervoussystem (CNS) tumor in adults, comprising one-third of all primary adult CNStumors. Although several recent publications have identified molecularalterations in meningioma including characteristic mutations, copy numberalterations, and gene expression signatures, our understanding of the drivers ofmeningioma recurrence is limited.Objective: To identify gene expression signatures of 1p-22q-NF2- meningiomarecurrence, with concurrent biallelic inactivation of NF2 and loss of chr1p that areheterogenous but enriched for recurrent meningiomas.Methods: Transcriptomic alterations present in recurrent versus primary 1p-22q-NF2- meningiomas were identified using RNA sequencing (RNA-seq) data in aclinically annotated cohort.Results: Recurrent 1p-22q-NF2- meningiomas were enriched for a newlyidentified GSTM1 null genotype compared to primary meningiomas thatshowed variable GSTM1 expression and independent external validationwas performed.Conclusions: The GSTM1 null genotype is a novel biomarker of 1p-22q-NF2-meningioma recurrence that resolves heterogeneity in existing meningiomasubtypes and may be used to guide future clinical management decisions onextent of treatment to improve patient outcomes.