Adult-Type Diffuse Gliomas

C71WHO Vol. 6 (CNS5, 2021)

Central Nervous System (CNS)

Prognosis

This section is being prepared by our editorial process.

🔬 Histological Types

📚 Latest Research

2026-09-10

The glioma metabolite, D-2-hydroxyglutarate (D-2-HG), reduces synaptic transmission and epileptiform bursts in neocortical slices.

Shao L, et al

Contrary to a widely held hypothesis, the glioma metabolite D-2-hydroxyglutarate (D-2-HG) does not promote seizures in brain tissue but instead reduces epileptiform burst frequency and suppresses excitatory synaptic transmission in neocortical slices. Using whole-cell patch-clamp electrophysiology, researchers tested acute bath application of D-2-HG (10 mM) on neocortical tissue preserving intact excitatory-inhibitory networks, finding that rather than depolarizing neurons or triggering seizure-like discharges, D-2-HG prolonged inter-burst intervals and diminished both mono- and poly-synaptic excitatory postsynaptic currents. This finding is clinically significant because approximately 80% of patients with IDH-mutant low-grade gliomas experience seizures, and nearly half of those cases are drug-refractory, meaning the assumed mechanism driving epilepsy in these patients must be reconsidered. The results challenge the glutamate-mimicry model and redirect the search for the true cause of seizures in this large population of glioma patients.

Experimental neurology

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2026-09-10

Human MutLα activates methylpurine DNA glycosylase to induce alkylation damage cytotoxicity.

Ashour ME, et al

Researchers have discovered that the mismatch repair (MMR) protein MutLα physically and functionally activates the base excision repair enzyme methylpurine DNA glycosylase (MPG), stimulating the removal of common alkylation DNA adducts such as 7meG and 3meA and thereby promoting cytotoxicity during alkylation chemotherapy. Biochemical reconstitution demonstrated that MutLα enhances MPG substrate binding and release from abasic site products — a process requiring ATP hydrolysis and the MLH1-interacting region on MPG — which facilitates enzyme turnover and increases alkylation-induced abasic sites in cells. These findings provide a new mechanistic explanation for why loss of MMR, a frequent event in glioblastoma, confers resistance to alkylating agents, complementing and challenging the long-standing futile repair cycle model. The newly uncovered cross-talk between MMR and base excision repair may inform strategies to overcome chemoresistance in diffuse gliomas and other tumors treated with alkylating chemotherapy.

Genes & development

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2026-09-10 • AI

A Transformer-Based Deep Learning Model for Prediction of Temozolomide Resistance in Glioblastoma Using Pretreatment MRI Images.

Xue C, et al

A Vision Transformer-based fusion model combining pretreatment MRI deep learning analysis with MGMT methylation status achieved AUC values of 0.855, 0.917, 0.806, and 0.848 across the training, internal validation, and two external validation cohorts, respectively, for predicting temozolomide (TMZ) resistance in glioblastoma. The study retrospectively enrolled 314 GBM patients from four centers between January 2021 and December 2024, selecting a 10 mm peritumoral expansion margin as optimal for the deep learning network. The fusion model outperformed both the standalone deep learning network and MGMT methylation status alone across all cohorts, with decision curve analysis confirming high net clinical benefit. This tool has the potential to spare TMZ-resistant patients from unnecessary chemotherapy while identifying those who may benefit from more aggressive treatment strategies.

Academic radiology

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