Integrated Clinical Genetic Analysis of Meningiomas Causing Bony Hyperostosis Shows More Severe Clinical Course and Overexpression of Secreted Pro-osteogenic Factors.

Abstract

Background and objectives: Meningiomas are the most common primary tumor of the brain and may elicit hyperostosis of the adjacent bone. Whether hyperostosis is related to reactive changes of the overlying bone or by invasion of the tumor itself is unclear. In this article, we characterize the clinical and molecular differences of meningiomas with hyperostosis from those without hyperostosis.

Methods: One hundred and eighty-one primary, nonsyndromic, nonradiation-induced meningiomas with DNA and RNA sequencing were included in a retrospective study. Preoperative MRI and computed tomography scans were reviewed by a fellowship-trained neuroradiologist to identify the presence of hyperostosis or bone invasion. Clinical, radiographic, and surgical data were gathered for each patient. Bulk RNA sequencing was performed, and data were analyzed for gene set enrichment analysis, gene ontologies, and differentially expressed genes along with chromosomal deletions and canonical mutations.

Results: Sixty-six (36.5%) meningiomas had radiographic evidence of hyperostosis compared with 115 (63.5%) without hyperostosis. Patients with hyperostosis had more severe presentation with increased rates of emergency department admissions (P = .0320) and seizure presentation (P = .0480). Hyperostotic tumors preferentially manifested in the olfactory groove location (P = .004). Radiographically, tumors with hyperostosis had higher rates of edema (P = .0280), midline shift (P = .010), nonhomogeneous enhancement (P = .001), T2 hyperechoic signal (P = .001), and bone invasion (P < .001). Patients with hyperostosis had increased estimated blood loss intraoperatively (P = .006), longer time in the operating room (P = .045), and higher rates of craniectomy and cranioplasty (P < .001 and P = .001). Fifty-five percent of all upregulated differentially expressed genes in hyperostotic tumors are secreted, and many are related to skeletal system development (BMP3, RBP4, MATN4, CILP2, and FGF7).

Conclusion: In a retrospective study, meningiomas with hyperostosis are region-specific, are related to higher intraoperative complications, and present with distinct radiographic features. Transcriptional analysis revealed upregulation of secreted proteins that positively influence bone development and growth.