204 Methylomic Analysis Identifies Three Groups of Spinal Meningiomas

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INTRODUCTION: Spinal meningiomas (SMs) are histologically similar to intracranial meningiomas (ICMs), but focused studies on SMs are uncommon. METHODS: This is a retrospective study of patients undergoing SM resection at our institution between 2010 and 2023. Clinical and radiographic characteristics were reviewed and analyzed with standard statistical methods. A Partitioning Around Medoids approach was used to cluster SMs with methylation data in a combined cohort from our institution and a publicly available dataset by methylation profiles. SMs were also classified based on a previously-developed ICM classifier. Clinical variables and pathway analyses were compared for the resulting clusters. RESULTS: Sixty-five SMs were resected in 53 patients with median radiographic follow-up of 34 months. Forty-six (87%) patients were female. The median age at surgery was 65 years and median tumor diameter was 1.9 cm. The five-year progression-free survival (PFS) rate was 90%, with subtotal resection being associated with recurrence or progression (p = .017). Compared to patients with ICMs, those with SMs were older (p = .036) and more likely to be female (p = .004). SMs clustered into hypermethylation, intermediate methylation, and hypomethylation subgroups. Tumors in the hypermethylated subgroup were associated with higher WHO Grade (p = .046) and higher risk histological subtypes (p < .001), while tumors in the hypomethylation subgroup were least likely to present with copy-number loss in chromosome 22q (p < .0001). SMs classified as immune-enriched under a previously developed ICM classifier did not have increased leukocyte fractions or hypomethylation of genes typically hypomethylated in immune-enriched tumors. CONCLUSIONS: SMs are more benign than their intracranial counterparts, and gross-total resection results in long term PFS. Methylation profiling of SMs identifies subgroups with differences in clinical variables.

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