Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas

Gray Umbach; Edwina B Tran; Charlotte D Eaton; Abrar Choudhury; Ramin Morshed; Javier E Villanueva-Meyer; Philip V Theodosopoulos; Stephen T Magill; Michael W McDermott; David R Raleigh; Ezequiel Goldschmidt

doi:10.1227/ons.0000000000001052

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas

Oper Neurosurg (Hagerstown). 2024 Jan 8. doi: 10.1227/ons.0000000000001052. Online ahead of print.

Authors

Gray Umbach¹, Edwina B Tran², Charlotte D Eaton¹, Abrar Choudhury^{1

3

4}, Ramin Morshed¹, Javier E Villanueva-Meyer^{1

5}, Philip V Theodosopoulos¹, Stephen T Magill⁶, Michael W McDermott⁷, David R Raleigh^{1

3

4

8}, Ezequiel Goldschmidt¹

Affiliations

¹ Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
² School of Medicine, University of California, San Francisco, San Francisco, California, USA.
³ Department of Radiation Oncology, University of California, San Francisco, San Francisco, California, USA.
⁴ Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
⁵ Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
⁶ Department of Neurological Surgery, Northwestern University, Chicago, Illinois, USA.
⁷ Miami Neuroscience Institute, Miami, Florida, USA.
⁸ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.

PMID: 38189372
DOI: 10.1227/ons.0000000000001052

Abstract

Background and objectives: Meningiomas are the most common primary intracranial tumors and are among the only tumors that can form lamellar, hyperostotic bone in the tumor microenvironment. Little is known about the epidemiology or molecular features of hyperostotic meningiomas.

Methods: Using a retrospective database of 342 meningiomas treated with surgery at a single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), and surgical variables with the presence of MIH using generalized linear models. Meningioma DNA methylation grouping was analyzed on a separate population of patients from the same institution with preoperative imaging studies sufficient for identification of MIH (n = 200).

Results: MIH was significantly correlated with anterior fossa (44.3% of MIH vs 17.5% of non-MIH were in the anterior fossa P < .001, c2) or skull base location (62.5% vs 38.3%, P < .001, c2) and lower MIB-1 labeling index. Gross total resection was accomplished in 27.3% of tumors with MIH and 45.5% of nonhyperostotic meningiomas (P < .05, t test). There was no association between MIH and histological World Health Organization grade (P = .32, c2). MIH was significantly more frequent in meningiomas from the Merlin-intact DNA methylation group (P < .05). Somatic missense mutations in the WD-repeat-containing domain of the TRAF7 gene were the most common genetic alteration associated with MIH (n = 12 of 15, 80%, P < .01, c2).

Conclusion: In this article, we show that MIH has a predilection for the anterior skull base and affected tumors are less amenable to gross total resection. We find no association between MIH and histological World Health Organization grade, but show that MIH is more common in the Merlin-intact DNA methylation group and is significantly associated with TRAF7 somatic missense mutations. These data provide a framework for future investigation of biological mechanisms underlying MIH.