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Molecular Characterization of Meningioma

ABSTRACT: Meningiomas are the most common primary tumors of the central nervous system. A majority of meningiomas have a relatively benign clinical course. However, even benign meningiomas can manifest with focal neurological symptoms or mass effect depending on the size and location of the tumor. Current standard of care for symptomatic tumors remains maximal safe surgical resection followed by radiological surveillance, with additional radiation therapy for high-grade tumors or tumors where complete resection is not feasible. To date, there is limited evidence demonstrating definitive efficacy of systemic therapies for meningiomas. Here, we perform full-transcriptome spot-resolution spatial transcriptomics using the 10X Visium platform on 19 low-grade meningiomas. We use bulk methylation profiling to classify these meningiomas into three previously described methylation classes corresponding to the Merlin-intact, immune-enriched, and hypermitotic molecular phenotypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE299027 | GEO | 2026/05/31

REPOSITORIES: GEO

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Project description:Meningiomas are typically considered a benign tumor that can be cured by complete surgical resection; however, a percentage of patients have recurrent disease, even after apparently complete resections. These patients require additional surgeries, radiation therapy, chemotherapy, or a combination of all three. The ability to recognize these patients prior to recurrence would promote earlier use of adjuvant therapy, thus improving overall patient outcome. Unfortunately, identification of meningiomas with this more aggressive phenotype is difficult, and standard histopathological techniques rarely suffice. The identification of genetic and molecular parameters that can help to define these more aggressive tumors would improve prognostication and treatment planning for patients with meningiomas. 1. Establish gene profiles for benign (grade 1) and aggressive (grades 2 and 3) meningiomas. 2. Determine if there are particular expression profiles that can help differentiate between benign and aggressive meningiomas. 3. Determine if there is/are specific gene(s) whose expression is/are altered in benign vs aggressive tumors. 4. Determine if there is a correlation between specific genetic abnormalities in these tumors (as analyzed by fluorescent in situ hybridization; FISH) and gene expression profiles. Our overall hypothesis is that there are molecular and biochemical changes that can be used to identify meningiomas that will have a more aggressive clinical course. Specific Aims 1 and 2: RNA from flash frozen or RNA-later preserved tissue (from all three grades of meningiomas) has been used for RNA isolation using standard protocols. RNA quantity has been determined using a RiboGreen RNA quantitation Kit (Molecular Probes), and RNA quality has been demonstrated using standard formaldehyde gels. These samples will be sent to the NINDS/NIMH microarray consortium for Affymetrix microarray analyses. Data analysis will be done using GeneSpring software (Silicon Genetics, Inc.) with assistance from consortium personnel. Specific Aim 3: Differentially expressed genes identified through microarray analyses will be analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Real time qRT-PCR is a standard technique used in our laboratory for gene expression analysis. Specific Aim 4: FISH analyses of paraffin-embedded tissue has been completed for 77 tumors. We have frozen tissue from a number of these patients. RNA from these samples will be used for microarray analyses (Specific Aims 1-3). The results of Speicifc Aims 1 and 2 will affect how we perform our correlation analyses. This will be done with the assistance of contracted statistical personnel

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Molecular Characterization of Meningioma

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