Gene mutations linked to drug-resistant epilepsy in astrocytoma.

IF 2.7 3区医学 Q2 CLINICAL NEUROLOGY

Frontiers in Neurology Pub Date : 2025-03-04 eCollection Date: 2025-01-01 DOI:10.3389/fneur.2025.1523468

Kanitpong Phabphal, Anukoon Kaewborisutsakul, Kittinun Leetanaporn, Pongsakorn Choochuen, Thara Tunthanathip, Raphatphorn Navakanitworakul, Surasak Sangkhathat

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引用次数: 0

Abstract

Introduction: Epilepsy is common in gliomas, particularly astrocytomas, even in patients who have undergone total tumor resection. Resistance to antiseizure drugs presents a significant challenge in managing epilepsy. Seizure outcomes after brain surgery for drug-resistant epilepsy (DRE) are heterogeneous and difficult to predict using models that evaluate current clinical, imaging, and electrophysiological variables. This study aimed to investigate possible correlations between genetic mutations and antiseizure resistance using whole-exome sequencing.

Methods: Tumor samples from a medical biobank were subjected to whole-exome sequencing, and the contribution of 64 genes from a previous report was analyzed.

Results: Fifteen patients had DRE. Compared to the patients who showed drug responsiveness, patients in the DRE group exhibited mutations in glutamate receptor genes (GRIA1, GRIK5, GRIN2B, or GRIN2C), ATRX, and the glutamate-S-transferase gene. No significant differences were found between the groups in terms of mutations in BRAF, Olig2, Ki-67, IDH, PIK3CA, p53, GRM, or BCL2A.

Discussion: These findings suggest that somatic gene mutations are closely linked to DRE. Identifying the molecular basis of antiseizure drug resistance is crucial for improving the management of DRE.

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导言：癫痫常见于胶质瘤，尤其是星形细胞瘤，即使是肿瘤已完全切除的患者。抗癫痫药物的耐药性是治疗癫痫的一大挑战。耐药性癫痫（DRE）脑部手术后的癫痫发作结果各不相同，很难通过评估当前临床、影像学和电生理学变量的模型进行预测。本研究旨在利用全外显子组测序技术研究基因突变与抗癫痫耐药性之间可能存在的相关性：方法：对一个医学生物库中的肿瘤样本进行全外显子组测序，并分析先前报告中的 64 个基因的贡献：结果：15 名患者患有 DRE。与表现出药物反应性的患者相比，DRE 组患者的谷氨酸受体基因（GRIA1、GRIK5、GRIN2B 或 GRIN2C）、ATRX 和谷氨酸-S-转移酶基因发生了突变。各组之间在BRAF、Olig2、Ki-67、IDH、PIK3CA、p53、GRM或BCL2A基因突变方面没有发现明显差异：这些研究结果表明，体细胞基因突变与 DRE 密切相关。确定抗癫痫药物耐药性的分子基础对于改善 DRE 的治疗至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Neurology CLINICAL NEUROLOGYNEUROSCIENCES -NEUROSCIENCES

CiteScore

4.90

自引率

8.80%

发文量

2792

审稿时长

14 weeks

期刊介绍： The section Stroke aims to quickly and accurately publish important experimental, translational and clinical studies, and reviews that contribute to the knowledge of stroke, its causes, manifestations, diagnosis, and management.