Integrated Genomic Analysis and Methylation Profiling of Thoracic Spinal Meningiomas

Introduction: Spinal meningiomas are less frequently diagnosed than intracranial meningiomas. While recent advancements in tumor biology have identified key driver genes in spinal meningiomas through targeted sequencing, few studies have yet to characterize the genomic profiles of these tumors together with their methylation signatures. In this study, we present a combined genomic and epigenetic analysis of 8 thoracic spinal meningiomas.

Methods: We performed targeted genomic sequencing on 8 primary spinal meningiomas using a 500-gene panel that includes known meningioma drivers and collected DNA methylation profiles from these patient samples. We further collected relevant clinical information and tumor imaging through retrospective chart review.

Results: All tumor samples were characterized as WHO Grade I intradural extramedullary meningiomas localized to the thoracic spine. Targeted DNA sequencing revealed mutations in meningioma-driver genes NF2 (62.5%), AKT1 (12.5%), and SMARCB1 (25%), in addition to several mutations yet to be described in literature on spinal meningiomas. DNA methylation profiling classified 6 samples with a benign signature and 2 with an intermediate signature. All patients were treated through surgical excision of the tumor, and clinical follow-up and imaging demonstrated no tumor recurrence or residual symptoms.

Conclusion : Our data, in concordance with prior studies, demonstrates a diverse genomic and epigenetic landscape of thoracic spinal meningiomas despite a seemingly homogenous clinical presentation. Understanding and identifying the molecular underpinnings can lead to a more precise and clinically significant classification of spinal meningiomas, which can further contribute to the development of targeted and improved therapeutic strategies.