Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity

Abstract In contrast to the relative morphological uniformity of histone H3 K27-mutant high-grade gliomas, H3 G34-mutant tumors present as a histopathologically heterogeneous group of neoplasms, with microscopic characteristics typical of either glioblastoma (GBM) or central nervous system primitive neuroectodermal tumors (CNS-PNET). In the current study, we performed an integrative clinical, histopathological and molecular analysis of 81 G34-mutant CNS tumors. Routinely prepared tumor tissues were investigated for genomic and epigenomic alterations. Despite their divergent histopathological appearance, CNS tumors with H3.3 G34 mutations displayed uniform epigenetic signatures, suggesting a single biological origin. Comparative cytogenetic analysis with other GBM subtypes disclosed a high frequency and high specificity of 3q and 4q loss across G34-mutant tumors. PDGFRA amplification was more common in cases with GBM than with PNET morphology (36 vs. 5 %, respectively), while CCND2 amplifications showed the opposite trend (5 vs. 27 %). Survival analysis revealed the presence of amplified oncogene(s) and MGMT methylation as independent prognostic markers for poor and favorable outcomes, respectively. No difference in outcome was found between morphological variants (GBM vs. PNET). Thus, different histological variants of G34-mutant CNS tumors likely comprise a single biological entity (high-grade glioma with H3 G34 mutation, HGG_G34), which should be outlined...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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CCR Grand Rounds Dr. Jabado ’ s research focuses on elucidating genetic signatures of pediatric astrocytomas and examining how they compare to adults. These are deadly brain tumors that originate in the brain and include glioblastomas (GBM, the highest grade of astrocytomas), which are one of the deadliest cancers in humans. Her group uncovered that pediatric high-grade astrocytomas (HGA) are molecularly and genetically distinct from adult tumors. They also identified a new molecular mechanism driving pediatric HGA, namely recurrent somatic driver mutations in the tail of histone 3 variants (H3.3 and H3.1). These mut...
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video
Conditions:   Brain Neoplasm;   Malignant Brain Glioma Interventions:   Drug: Gadobenate Dimeglumine;   Drug: Gadobutrol;   Procedure: Magnetic Resonance Imaging Sponsors:   M.D. Anderson Cancer Center;   National Cancer Institute (NCI) Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
To predict vascular endothelial growth factor (VEGF) expression in patients with diffuse gliomas using radiomic analysis.
Source: Cancer Imaging - Category: Radiology Authors: Tags: Research article Source Type: research
ConclusionsCAM are frequently used by glioma patients in France. Underlying needs and expectations, as well as potential interactions with tumor-specific treatments, and financial and quality of life burden, should be discussed with patients and caregivers.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
Conclusions. In summary, RES529, the first dual TORC1/TORC2 dissociative inhibitor, lacking affinity for ABCB1/ABCG2 and having good brain penetration, was active in GBM preclinical/murine models giving credence to its use in clinical trial for patients with GBM treated in association with anti-angiogenetic compounds.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Publication date: Available online 19 October 2019Source: NeuroImage: ClinicalAuthor(s): Binke Yuan, Nan Zhang, Jing Yan, Jingliang Cheng, Junfeng Lu, Jinsong WuAbstractLanguage deficits following brain tumors should consider the dynamic interactions between different tumor growth kinetics and functional network reorganization. We measured the resting-state functional connectivity of 126 patients with left cerebral gliomas involving language network areas, including 77 patients with low-grade glioma (LGG) and 49 patients with high-grade glioma (HGG). Functional network mapping for language was performed by construction of ...
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
ConclusionsConventional MRI radiomics models are reliable for predicting the MGMT promoter methylation status in LGG patients. The fusion of radiomics features from different series may increase the prediction performance.
Source: European Journal of Radiology - Category: Radiology Source Type: research
Parents of Abbie Mifsud created the charity that has funded vital research on brain stem tumoursResearchers say they are close to testing a drug that could tackle a previously untreatable childhood brain cancer. The condition is known as DIPG – diffuse intrinsic pontine glioma – and every year it affects between 30 to 40 boys and girls, aged between five and 10. All develop tumours caused by the condition and die, often within months of their diagnoses.But now scientists believe they may soon be able to tackle the condition – and one of the key organisations involved is a remarkable charity set up by Aman...
Source: Guardian Unlimited Science - Category: Science Authors: Tags: Drugs Health Science Society UK news Source Type: news
CONCLUSION: Radiolabelled PSMA imaging seems to be useful in analyzing glioma/glioblastoma. Further studies enrolling a wider population are needed to clarify the real clinical and diagnostic role of radiolabelled PSMA in this setting and its possible position in the diagnostic flow-chart. PMID: 31625482 [PubMed - as supplied by publisher]
Source: Current Radiopharmaceuticals - Category: Radiology Tags: Curr Radiopharm Source Type: research
This study aims to investigate genetic alterations within EEF1A1, EEF1A2, EEF1B2, EEF1D, EEF1E1 and EEF1G genes and their potential effects on epigenetic regulation mechanisms.Materials and methodsIn this study, we analyzed DNA sequencing and mRNA expression data available on The Cancer Genome Atlas (TCGA) across different cancer types to detect genetic alterations in EEF1 genes and investigated their potential impact on selected epigenetic modulators.Key findingsWe found that EEF1 complex proteins were deregulated in several types of cancer. Lower EEF1A1, EEF1B2, EEF1D and EEF1G levels were correlated with poor survival i...
Source: Life Sciences - Category: Biology Source Type: research
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