We hypothesize that the primary cell pool isolated from LGG tumor contains a heterogeneous population consisting tumor cells at various stages of tumor progression including cells with early genetic lesions if any prior to acquisition of IDH1 mutation.
This theory also provides an explanation for some of the most perplexing observations, including the scarcity of proper model systems and the prevalence of IDH1 mutation in glioma.
T1+Gad performed best for IDH typing of glioblastoma (sensitivity 91.9%, specificity 100%, AUC 0.945) and ADC for non-Gadolinium-enhancing gliomas (sensitivity 85.7%, specificity 78.4%, AUC 0.877).
<sup>1</sup> H-MRS enables non-invasive detection of 2-hydroxyglutarate (2-HG), an oncometabolite accumulating in gliomas carrying mutations in the isocitrate dehydrogenase (IDH) genes.
In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation.
Mutation of the isocitrate dehydrogenase (IDH) gene and co-deletion on chromosome 1p/19q is becoming increasingly relevant for the evaluation of clinical outcome in glioma.
Moreover, MEOX2 expression was associated with IDH1/2 wildtype molecular subtype and was significantly correlated with overall survival of all gliomas and, more interestingly, in lower grade glioma.
In 1 case, an IDH1R132H-mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report.
IDH1/2 active site mutations confer a neomorphic enzyme activity producing the oncometabolite D-2-hydroxyglutarate (D-2HG), which generates the glioma CpG island methylation phenotype (G-CIMP).
The mini-column method enables rapid identification of 2-HG, providing a promising strategy for intraoperative diagnosis of IDH1-mutated gliomas in the future.