An Institutional Experience of Genomic Analysis and Methylation Profiling of Thoracic Spinal Meningiomas

Abstract

Objective: Spinal meningiomas (SMs) are less frequently diagnosed than intracranial meningiomas. While recent advancements in tumor biology have identified key driver genes in SMs 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 our institutional experience of a combined genomic and epigenetic analysis of 8 thoracic SMs.

Methods: We performed targeted genomic sequencing and DNA methylation profiling on 8 primary SMs. We further collected relevant clinical information and tumor imaging through a retrospective chart review.

Results: All tumor samples were characterized as World Health Organization Grade I intradural extramedullary meningiomas localized to the thoracic spine. Targeted genomic sequencing revealed mutations in meningioma-driver genes Neurofibromatosis type 2 (62.5%), AKT1 (12.5%), and SMARCB1 (25%), in addition to several mutations in genes involved in various signaling pathways. 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 significant residual symptoms.

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

Keywords: Genetics; Spine; Tumor.