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      Recent Advances in Meningioma Immunogenetics

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          Abstract

          Meningiomas are relatively common, and typically benign intracranial tumors, which in many cases can be cured by surgical resection. However, less prevalent, high grade meningiomas, grow quickly, and recur frequently despite treatment, leading to poor patient outcomes. Across tumor grades, subjective guidelines for histological analysis can preclude accurate diagnosis, and an insufficient understanding of recurrence risk can cloud the choice of optimal treatment. Improved diagnostic and prognostic markers capable of discerning between the 15 heterogeneous WHO recognized meningioma subtypes are necessary to improve disease management and identify new targeted drug treatments. In this review, we show the advances in molecular profiling and immunophenotyping of meningiomas, which may lead to the development of new personalized therapeutic strategies.

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          Most cited references89

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          The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

          The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
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            Regulatory T cells, tumour immunity and immunotherapy.

            Tumours express a range of antigens, including self-antigens. Regulatory T cells are crucial for maintaining T-cell tolerance to self-antigens. Regulatory T cells are thought to dampen T-cell immunity to tumour-associated antigens and to be the main obstacle tempering successful immunotherapy and active vaccination. In this Review, I consider the nature and characteristics of regulatory T cells in the tumour microenvironment and their potential multiple suppressive mechanisms. Strategies for therapeutic targeting of regulatory T cells and the effect of regulatory T cells on current immunotherapeutic and vaccine regimens are discussed.
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              Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.

              We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                08 January 2020
                2019
                : 9
                : 1472
                Affiliations
                [1] 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University , Riyadh, Saudi Arabia
                [2] 2Inova Neuroscience and Spine Institute, Inova Health Systems , Falls Church, VA, United States
                [3] 3Virginia Commonwealth University School of Medicine, Inova Campus , Richmond, VA, United States
                [4] 4Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City, King Abdulaziz City for Science and Technology , Riyadh, Saudi Arabia
                Author notes

                Edited by: Theodore Nicolaides, New York University, United States

                Reviewed by: David M. Peereboom, Case Western Reserve University, United States; Sunit Das, St. Michael's Hospital, Canada

                *Correspondence: Malak Abedalthagafi malthagafi@ 123456kfmc.med.sa

                This article was submitted to Neuro-Oncology and Neurosurgical Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2019.01472
                6960175
                31970090
                c80d1fa7-18b4-4f26-bc6b-581010e35a73
                Copyright © 2020 Al-Rashed, Foshay and Abedalthagafi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 October 2019
                : 09 December 2019
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 89, Pages: 11, Words: 8930
                Funding
                Funded by: King Fahad Medical City 10.13039/501100011680
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                meningioma,ngs,genomics,immunotherapy,neuro-oncology,personalized medicine
                Oncology & Radiotherapy
                meningioma, ngs, genomics, immunotherapy, neuro-oncology, personalized medicine

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