378 Meningiomas Causing Bony Hyperostosis Upregulate Cell Adhesion, Bone Mineralization, and Bone Development Gene Signatures

Abstract

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Some meningiomas cause hyperostosis of the adjacent bone, affecting surgical approach. METHODS: Two hundred twelve meningioma MRIs were reviewed by a neuroradiologist to classify location and hyperostosis or bone involvement. These tumors were bulk RNA sequenced and analyzed with gene sets enrichment analysis (GSEA), gene ontologies (GO), and differentially expressed genes (DEGs). RESULTS: Sixty-seven meningiomas had hyperostosis detected in imaging compared to 145 without it. Meningiomas with hyperostosis occurred most commonly in the sphenoid wing and lateral skull base and relatively less commonly in the clinoidal and clival region (p-val = 0.033, Fisher’s Exact). Looking at the distribution throughout MenG groups, a multi-omic classifier used to predict recurrence, meningiomas with hyperostosis occurred more frequently in the MenG A and MenG C groups compared to MenG B group (p-val = 0.0299, Fisher’s Exact). This may reflect previously described similarity in transcriptional signatures of group A and C. GO analysis revealed upregulation of skeletal system development, peptide breakdown, cell adhesion, and collagen biological processes in hyperostotic tumors (a.,p-val < 0.05), and downregulation of synaptic signaling and receptor activity (b.,p-val < 0.05). When analyzing only genes that were significantly upregulated (padj < 0.05), GOs related to skeletal system development, cellular movement, and hydrogen peroxide processing were upregulated. Alternatively, synaptic transport and negative regulation of peptide breakdown were downregulated. Specific upregulated genes include MEPE, a bone mineralization gene, and cell migration genes like NYAP2, TNS4, and GPM6A (Log2FC > 1, padj < 0.05). CONCLUSIONS: Meningiomas with hyperostosis occurred more frequently in the sphenoid wing and lateral skull base. MenG B tumors were least likely to cause hypoerostosis, Meningiomas causing hypoerostosis have unique transcriptional signatures related to bone involvement and cell motility, matching their invasive phenotype.