An analysis of 2589 patient samples showed that CLEC5A expression is higher in (1) glioblastoma than in lower-grade glioma and nontumor tissue, (2) in the mesenchymal subtype than in other subtypes, and (3) in IDH1-wild type glioblastoma than in IDH1-mutated glioblastoma.
To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts.
Taken together, these results underscore the functional importance of IDH1 mutation heterozygosity in glioma biology and indicate functional loss of mutant IDH1 as an escape mechanism underlying glioma progression and the pathway of redox homeostasis as potential therapeutic targets.
Twenty-five glioma cases were positive for IDH1 mutations by COLD-PCR/FMCA, and 23 gliomas were positive by the conventional real-time PCR and Sanger sequencing.
Our data also confirm the prognostic impact of IDH1/IDH2 mutation in gliomas whatever grade considered: patients harboring mutations of IDH1/IDH2 have an improved median overall survival.
Mutant IDH1 results in the production of a metabolite 2-hydroxyglutarate (2-HG) that can inhibit DNA and histone demethylating enzymes resulting in the glioma-CpG island phenotype (G-CIMP) and increased histone methylation marks.
In summary, our findings suggest that cMYC may be associated with a unique clinicopathologic and biologic group of infiltrating gliomas and help mediate the malignant transformation of IDH1 mutant gliomas.
For instance, mutations in the <i>isocitrate dehydrogenase 1 (IDH1)</i> gene, which occurs in a subgroup of glioma, correlate with risk of VTE, with low incidence in patients with presence of an <i>IDH1</i> mutation compared with those with <i>IDH1</i> wild-type status.
We sequenced IDH1 at codon 132 and IDH2 at codon 172 in 33 patients with WHO grade II and III gliomas who benefited from a preoperative (18)F-FDG positron emission tomography (PET).
In this study, using our mouse model and primary patient-derived glioma cultures with IDH1 mutations, we investigated the function of IDH1<sup>R132H</sup> in the context of TP53 and ATRX loss.
Interestingly, proteins regulated by phosphoinositide 3-kinase (PI3K)/Akt signaling, are among the top downregulated genes in gliomas associated with high percentage of IDH1 and IDH2 mutations.
Our observations support the hypothesis that IDH1 mutation may correlate with the benefit from VEGF(R)- versus EGFR-targeted therapy at the time of recurrence in glioma patients.
The current study aimed to perform a comprehensive meta-analysis to investigate the correlation of isocitrate-dehydrogenase 1 (IDH1), an important molecular biomarker for glioma classification and prognosis, to preoperative seizure incidence in LGG.