Isocitrate dehydrogenase (IDH) mutations produce high levels of the 'oncometabolite' R-2-hydroxyglutarate (R-2-HG) and play a key role in the initiation and progression of glioma tumors in the brain. A recent study in Nature Cancer by Friedrich et al. describes how IDH-mutant-derived R-2-HG elicits an immunosuppressive phenotype in glioma-associated macrophages. As such, the authors uncovered a new vulnerability that can be exploited for therapy.
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Glioma Image-Level and Slide-Level Gene Predictor (GLISP) for Molecular Diagnosis and Predicting Genetic Events of Adult Diffuse Glioma.
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Department of Pathology, University of Yamanashi, Yamanashi 409-3898, Japan.
The latest World Health Organization (WHO) classification of central nervous system tumors (WHO2021/5th) has incorporated molecular information into the diagnosis of each brain tumor type including diffuse glioma. Therefore, an artificial intelligence (AI) framework for learning histological patterns and predicting important genetic events would be useful for future studies and applications. Using the concept of multiple-instance learning, we developed an AI framework named GLioma Image-level and Slide-level gene Predictor (GLISP) to predict nine genetic abnormalities in hematoxylin and eosin sections: , , mutations, promoter mutations, homozygous deletion (CHD), amplification (amp), 7 gain/10 loss (7+/10-), 1p/19q co-deletion, and promoter methylation.
View Article and Find Full Text PDFPrediction of isocitrate dehydrogenase mutation status in WHO grade II glioma by diffusion kurtosis imaging.
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First Hospital of Shanxi Medical University, Shanxi, China.
Purpose: Isocitrate dehydrogenase (IDH) mutation status serves as a crucial prognostic indicator for glioma, typically assessed via immunohistochemical analysis post-surgery. Given the invasiveness of this approach, perhaps we can utilise convenient and noninvasive magnetic resonance imaging (MRI) methods to predict IDH mutation status. However, the current landscape lacks a standardised MRI technique for accurately predicting IDH mutations.
View Article and Find Full Text PDFManagement of Low-Grade Gliomas.
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From the Division of Neuro-Oncology, Department of Neurology and the Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians & Surgeons and NewYork-Presbyterian, New York, NY.
The term "low-grade glioma" historically refers to adult diffuse gliomas that exhibit a less aggressive course than the more common high-grade gliomas. In the current molecular era, "low-grade" refers to World Health Organization central nervous system grade 2 gliomas almost always with an isocitrate dehydrogenase (IDH) mutation (astrocytomas and oligodendrogliomas). The term "lower-grade gliomas" has emerged encompassing grades 2 and 3 IDH-mutant astrocytomas and oligodendrogliomas, to acknowledge that histological grade is not as important a prognostic factor as molecular features, and distinguishing them from grade 4 glioblastomas, which lack an IDH mutation.
View Article and Find Full Text PDFConcurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription.
Acta Neuropathol
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Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.
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