Glioblastoma: pathology, molecular mechanisms and markers

Abstract Recent advances in genomic technology have led to a better understanding of key molecular alterations that underlie glioblastoma (GBM). The current WHO-based classification of GBM is mainly based on histologic features of the tumor, which frequently do not reflect the molecular differences that describe the diversity in the biology of these lesions. The current WHO definition of GBM relies on the presence of high-grade astrocytic neoplasm with the presence of either microvascular proliferation and/or tumor necrosis. High-throughput analyses have identified molecular subtypes and have led to progress in more accurate classification of GBM. These findings, in turn, would result in development of more effective patient stratification, targeted therapeutics, and prediction of patient outcome. While consensus has not been reached on the precise nature and means to sub-classify GBM, it is clear that IDH-mutant GBMs are clearly distinct from GBMs without IDH1/2 mutation with respect to molecular and clinical features, including prognosis. In addition, recent findings in pediatric GBMs regarding mutations in the histone H3F3A gene suggest that these tumors may represent a 3rd major category of GBM, separate from adult primary (IDH1/2 wt), and secondary (IDH1/2 mut) GBMs. In this review, we describe major clinically relevant genetic and epigenetic abnormalities in GBM—such as mutations in IDH1/2, EGFR, PDGFRA, and NF1 genes—altered methylation of MGMT gen...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Purpose of review The current review summarizes recent advances on three important issues in neurofibromatosis type 1 (NF1) management: the identification of specific NF1 gene mutations predicting the risk for developing neurological malignancies; the molecular features of NF1-associated tumors and their differences from sporadic neoplasms; genetic, epigenetic, or microenviromental factors leading benign tumors to a malignant transformation in NF1. Recent findings The association between the risk of developing optic pathway glioma and specific germiline NF1 mutations is still debated and further studies are needed wit...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: BRAIN AND NERVOUS SYSTEM: Edited by Marc Sanson Source Type: research
aliga S, Yeap BY, Berrington de Gonzalez A, Yock TI Abstract OBJECTIVE: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. METHODS AND MATERIALS: Current eligibility criteria are radiotherapy patients
Source: The British Journal of Radiology - Category: Radiology Authors: Tags: Br J Radiol Source Type: research
In conclusion, CK2 appears to play a role not only in malignant glioma cells but it can also sustain the viability and proliferation of benign astrocytoma cells. The obtained antitumor effects of CK2 inhibitors significantly exceeded their mild or no effect on normal astrocytes in control, which supports the therapeutic potential of these compounds against gliomas. PMID: 31588710 [PubMed - in process]
Source: Folia Neuropathologica - Category: Neurology Tags: Folia Neuropathol Source Type: research
Conclusion: Mesial temporal LGGs are not alone and a high proportion of temporal neocortex appeared normal on preoperative MRI, may contain dual pathology. Thus, anterior temporal resection should be performed to have satisfactory seizure and oncological outcomes. PMID: 31583167 [PubMed]
Source: Surgical Neurology International - Category: Neurosurgery Tags: Surg Neurol Int Source Type: research
Conclusion: Although cases of concurrent glioma and MS remain rare, we present a case illustrating this phenomenon and explore a number of theories behind a potential causal relationship. PMID: 31583163 [PubMed]
Source: Surgical Neurology International - Category: Neurosurgery Tags: Surg Neurol Int Source Type: research
Publication date: Available online 4 October 2019Source: Interdisciplinary NeurosurgeryAuthor(s): Andrii Sirko, Lyudmila Dzyak, Ekaterina Chekha, Tetiana Malysheva, Dmytro RomanukhaAbstractIn the present report, a review of the literature on the combination of multiple sclerosis and brain tumours is performed. Additionally, the frequency of such combination, possible etiopathogenetic mechanisms, current diagnostic criteria and treatment approaches are reviewed. Furthermore, the case of a 30-year-old man with multiple sclerosis and anaplastic astrocytoma of the right temporal lobe is described in detail. Specifically, the p...
Source: Interdisciplinary Neurosurgery - Category: Neurosurgery Source Type: research
ConclusionsOur research demonstrates there is no uniform approach to the management of elderly patient with glioblastoma among academic neuro-oncologist.Legal entity responsible for the studyGEINO (Grupo Espa ñol de Investigación en Neurooncología).FundingHas not received any funding.DisclosureM. Vaz Salgado: Advisory / Consultancy, Travel / Accommodation / Expenses: Pharmamar; Advisory / Consultancy: Lilly, Eisai y Celgene; Research grant / Funding (self): Pfizer. M. Vieito Villar: Travel / Accommodation / Expenses: Roche. R. Luque: Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag; H...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
This study aims to describe characteristics and patterns of care of elderly patients with IDHm HGG included in the French POLA network dedicated to HGG.MethodsThe characteristics and patterns of care of elderly ( ≥70 years) patients IDHm HGG were compared to those of younger patients (
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsBAY is well tolerated as anticipated due to specificity for mIDH1. BAY inhibited mIDH1-R132X activity as evidenced by a PD effect in pts with measurable 2-HG, with objective response in 3 pts (all gliomas).Clinical trial identificationNCT02746081.Editorial acknowledgementMedical writing assistance was provided by Laura Valenzo, PhD, of Complete Health Vizion and funded by Bayer AG.Legal entity responsible for the studyBayer AG.FundingBayer AG.DisclosureW. Wick: Non-remunerated activity/ies, patent: IDH vaccine; Non-remunerated activity/ies, patent: IDH diagnostic; Non-remunerated activity/ies, patent: APG diagno...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundIn the phase III RTOG 9802 trial, median overall survival (OS) increased from 7.8 years with radiotherapy alone to 13.3 years (P = .002) with adjuvant procarbazine, lomustine, and vincristine (PCV) following surgery for low grade glioma. Although the PCV regimen improved survival, there were significant toxicities. We hypothesised more frequent toxicities would be observed in clinical practice. We aimed to identify and quantify toxicities in the real world setting in a National Neuro-Oncology centre.MethodsPatients with low grade glioma who received PCV following radiotherapy from Nov 2014 to Nov 2018 wer...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
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