Molecular neuropathology of brain‐invasive meningiomas

Spreckelsen, Niklas von; Kesseler, Christoph; Brokinkel, Benjamin; Goldbrunner, Roland; Perry, Arie; Mawrin, Christian

doi:10.1111/bpa.13048

Cited by 12 publications

(8 citation statements)

References 111 publications

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“…[ 34 ] Currently, only a limited number of experimental systems are available to study brain invasion by meningiomas. [ 35 ] Our findings may provide additional insights into the factors driving brain invasion and a reliable in vivo model to support future studies.…”

Section: Discussionmentioning

confidence: 87%

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA‐Seq

Huang

et al. 2023

Advanced Science

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High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1 + ) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1 + and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1 + in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.

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Section: Discussionmentioning

confidence: 87%

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA‐Seq

Huang

et al. 2023

Advanced Science

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“…Such alterations result in increased extracellular matrix degradation and inhibition of intercellular adhesion, leading to the epithelial–mesenchymal transition phenomenon associated with the tendency of the tumor to infiltrate. In a recent paper, von Spreckelsen and colleagues [ 61 ] highlighted that transcription factors and micro RNAs (mi-RNAs) have also been shown to play a role in BI of meningiomas through post-transcriptional modification, with particular attention to miR145, Let-7d, miR-18a, and miR-200a. Interestingly, different mechanisms play a role between BI and bone invasion in some meningioma subtypes, depending on tumor location and genomic features and, among them, NF-2 and TRAF7 mutations [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Updated Systematic Review on the Role of Brain Invasion in Intracranial Meningiomas: What, When, Why?

Brunasso

Bonosi

Costanzo

et al. 2022

Cancers

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Several recent studies are providing increasing insights into reliable markers to improve the diagnostic and prognostic assessment of meningioma patients. The evidence of brain invasion (BI) signs and its associated variables has been focused on, and currently, scientific research is investing in the study of key aspects, different methods, and approaches to recognize and evaluate BI. This paradigm shift may have significant repercussions for the diagnostic, prognostic, and therapeutic approach to higher-grade meningioma, as long as the evidence of BI may influence patients’ prognosis and inclusion in clinical trials and indirectly impact adjuvant therapy. We intended to review the current knowledge about the impact of BI in meningioma in the most updated literature and explore the most recent implications on both clinical practice and trials and future directions. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a complete overview of characteristics, preoperative applications, and potential implications of BI in meningiomas. Nineteen articles were included in the present paper and analyzed according to specific research areas. The detection of brain invasion could represent a crucial factor in meningioma patients’ management, and research is flourishing and promising.

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“…Even in microscopic surgery, it penetrates the arachnoid interface or encases cerebral blood vessels [ 8 ]. An important structure that supports or prevents brain involvement is the so-called “brain-meningioma interface.” It can be divided into three types: bone invasion, perivascular growth along the Virchow-robin-spaces, and direct brain invasion [ 13 ].…”

Section: Brain Invasive Meningiomamentioning

confidence: 99%

Brain Invasion and Trends in Molecular Research on Meningioma

Kim

2023

Brain Tumor Res Treat

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Meningiomas are the most common primary brain tumors in adults. The treatment of non-benign meningiomas remains a challenging task, and after the publication of the 2021 World Health Organization classification, the importance of molecular biological classification is emerging. In this article, we introduce the mechanisms of brain invasion in atypical meningioma and review the genetic factors involved along with epigenetic regulation. First, it is important to understand the three major steps for brain invasion of meningeal cells: 1) degradation of extracellular matrix by proteases, 2) promotion of tumor cell migration to resident cells by adhesion molecules, and 3) neovascularization and supporting cells by growth factors. Second, the genomic landscape of meningiomas should be analyzed by major categories, such as germline mutations in NF2 and somatic mutations in non- NF2 genes ( TRAF7 , KLF4 , AKT1 , SMO , and POLR2A ). Finally, epigenetic alterations in meningiomas are being studied, with a focus on DNA methylation, histone modification, and RNA interference. Increasing knowledge of the molecular landscape of meningiomas has allowed the identification of prognostic and predictive markers that can guide therapeutic decision-making processes and the timing of follow-up.

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Molecular neuropathology of brain‐invasive meningiomas

Cited by 12 publications

References 111 publications

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA‐Seq

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA‐Seq

Updated Systematic Review on the Role of Brain Invasion in Intracranial Meningiomas: What, When, Why?

Brain Invasion and Trends in Molecular Research on Meningioma

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