Molecular determinants of outcomes in meningiomas

Lynes, John; Flores-Milan, Gabriel; Rubino, Sebastian; Arrington, J.; Macaulay, Robert J.B.; Liu, James K.; Beer‐Furlan, André; Tran, Nam; Vogelbaum, Michael A.; Etame, Arnold B.

doi:10.3389/fonc.2022.962702

Cited by 5 publications

(5 citation statements)

References 82 publications

(70 reference statements)

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“…17 Hyperostotic Meningioma DNA Methylation Grouping DNA methylation profiling was analyzed in the context of MIH in a population of 91 patients with meningiomas that equally represented all histological WHO grades (Table 4). 4 To do this, we divided tumors between those with and without MIH (including osteolytic lesions, tumors that induced bone remodeling, and tumors that did not affect bony architecture). This analysis yielded 72 Merlin-intact, 65 Immune-enriched, and 63 Hypermitotic meningiomas, 21/200 (10.5 %) of which are hyperostotic.…”

Section: Next-generation Targeted Dna Sequencing Of Hyperostotic Vers...mentioning

confidence: 99%

“…Recently, next-generation sequencing and DNA methylation profiling have provided new insights into meningioma biology. 3,4 Cytogenic studies show that meningiomas with biallelic inactivation of the NF2 tumor suppressor encoding the Merlin protein on chromosome 22q can harbor significant copy number variants deleting or amplifying large regions of the genome. 5 Instead of copy number variants, Merlin-intact meningiomas are associated with recurrent somatic missense variants in genes such as TRAF7 , KLF4 , AKT1 , SMO , PIK3CA , and POLR2A , 6-9 and some of these genetic alterations have been identified in tumors with MIH.…”

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confidence: 99%

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Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas

Umbach,

Tran,

Eaton

et al. 2024

Operative Neurosurgery

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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.

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Section: Next-generation Targeted Dna Sequencing Of Hyperostotic Vers...mentioning

confidence: 99%

mentioning

confidence: 99%

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas

Umbach,

Tran,

Eaton

et al. 2024

Operative Neurosurgery

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“…81 Lynes et al summarized findings on current clinical trials investigating medical therapy in meningiomas. 82 Early results using immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab, and avelumab suggest clinically meaningful responses, 80 though most of the ongoing clinical trials are still in the recruiting phase and will not be completed until 2027 or thereafter. These trials are being conducted in the United States, France, Switzerland, and China, and are primarily evaluating PFS, toxicity, gene expression following drug administration, immunogenicity, changes in tumor size, and radiological response rates.…”

Section: Treatment Modalitiesmentioning

confidence: 99%

The Natural History and Treatment of Meningiomas: An Update

Nyalundja,

Mugisha,

Karekezi

2023

Semin Neurol

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Meningiomas are the most frequent nonmalignant tumors of the central nervous system (CNS). Despite their benign nature and slow-growing pattern, if not diagnosed early, these tumors may reach relatively large sizes causing significant morbidity and mortality. Some variants are located in hard-to-access locations, compressing critical neurovascular structures, and making the surgical management even more challenging. Although most meningiomas have a good long-term prognosis after treatment, there are still controversies over their management in a subset of cases. While surgery is the first-line treatment, the use of fractionated radiotherapy or stereotactic radiosurgery is indicated for residual or recurrent tumors, small lesions, and tumors in challenging locations. Advances in molecular genetics and ongoing clinical trial results have recently helped both to refine the diagnosis and provide hope for effective biomolecular target-based medications for treatment. This article reviews the natural history and current therapeutic options for CNS meningiomas.

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“…Histopathological categories of meningioma by grading: grade 1 is called benign, grade 2 is atypical, and grade 3 is malignant/anaplastic by WHO Classification of CNS Tumors 2021 6,7 . In grade classifications, invasion, necrosis, prominent nucleoli, high cellularity, and a high nuclear/cytoplasmic ratio are histologically important 8 . The histopathological classification of meningiomas and their characteristics according to grades are given in Table 1.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 In grade classifications, invasion, necrosis, prominent nucleoli, high cellularity, and a high nuclear/cytoplasmic ratio are histologically important. 8 The histopathological classification of meningiomas and their characteristics according to grades are given in Table 1.…”

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confidence: 99%

Related mechanisms, current treatments, and new perspectives in meningioma

Inetas‐Yengin,

Bayrak

2024

Genes Chromosomes & Cancer

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Meningiomas are non‐glial tumors that are the most common primary brain tumors in adults. Although meningioma can possibly be cured with surgical excision, variations in atypical/anaplastic meningioma have a high recurrence rate and a poor prognosis. As a result, it is critical to develop novel therapeutic options for high‐grade meningiomas. This review highlights the current histology of meningiomas, prevalent genetic and molecular changes, and the most extensively researched signaling pathways and therapies in meningiomas. It also reviews current clinical studies and novel meningioma treatments, including immunotherapy, microRNAs, cancer stem cell methods, and targeted interventions within the glycolysis pathway. Through the examination of the complex landscape of meningioma biology and the highlighting of promising therapeutic pathways, this review opens the way for future research efforts aimed at improving patient outcomes in this prevalent intracranial tumor entity.

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Molecular determinants of outcomes in meningiomas

Cited by 5 publications

References 82 publications

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas

The Natural History and Treatment of Meningiomas: An Update

Related mechanisms, current treatments, and new perspectives in meningioma

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