Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

SIMPLE SUMMARY: MRI and histological assessment remain the gold standard for meningioma diagnosis. Currently, WHO grading of meningiomas mainly depends on histologic and morphological markers and two molecular markers. WHO grading can reliably diagnose meningiomas in most cases. However, it was not as dependable in predicting prognosis, especially time to recurrence of Grade 1 and 2 meningiomas. This warrants the integration of new biomarkers into the current WHO grading system of meningiomas. Future meningioma biomarkers need to utilize an array of molecular technologies for biomarkers discovery, including genomic, epigenetic, proteomis, metabolomic, and RNA biomarkers, as well as a panel format to complement the existing WHO grading. The majority of candidate meningioma molecular biomarkers are still experimental and need to undergo testing in clinical trials, but their application in meningioma diagnosis will be necessary to guide future targeted therapies of meningiomas. ABSTRACT: Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas’ tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.