Low-grade neuroepithelial tumors are major causes of drug-resistant focal epilepsy. Clinically, these tumors are defined as low-grade epilepsy-associated neuroepithelial tumors (LEATs). The BRAF V600E mutation is frequently observed in LEAT and linked to poor seizure outcomes. However, its molecular role in epileptogenicity remains elusive. To understand the molecular mechanism underlying the epileptogenicity in LEAT with the BRAF V600E genetic mutation (BRAF V600E-LEAT), we conducted RNA sequencing (RNA-seq) analysis using surgical specimens of BRAF V600E-LEAT obtained and stored at a single institute. We obtained 21 BRAF V600E-LEAT specimens and 4 control specimens, including 24 from Japanese patients and 1 from a patient of Central Asian origin, along with comprehensive clinical data. We submitted the transcriptome dataset of 21 BRAF V600E-LEAT plus 4 controls, as well as detailed clinical information, to a public database. Preliminary bioinformatics analysis using this dataset identified 2134 differentially expressed genes between BRAF V600E-LEAT and control. Additionally, gene set enrichment analysis provided novel insights into the association between estrogen response-related pathways and the epileptogenicity of BRAF V600E-LEAT patients. Our datasets and findings will contribute toward the understanding of the pathology of epilepsy caused by LEAT and the identification of new therapeutic targets.

中文翻译：

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具有与致癫痫相关的 BRAF V600E 突变的低级别神经上皮肿瘤的转录特征

低度恶性神经上皮肿瘤是耐药局灶性癫痫的主要原因。临床上，这些肿瘤被定义为低度癫痫相关神经上皮肿瘤（LEAT）。BRAF V600E 突变在 LEAT 中经常观察到，并与不良癫痫结果相关。然而，其在致癫痫性中的分子作用仍然难以捉摸。为了了解带有BRAF V600E 基因突变的 LEAT（BRAF V600E-LEAT）致癫痫的分子机制，我们使用在单一研究所获得并储存的 BRAF V600E-LEAT 手术标本进行了 RNA 测序（RNA-seq）分析。我们获得了 21 份 BRAF V600E-LEAT 标本和 4 份对照标本，其中 24 份来自日本患者，1 份来自中亚裔患者，以及全面的临床数据。我们向公共数据库提交了 21 个 BRAF V600E-LEAT 和 4 个对照的转录组数据集以及详细的临床信息。使用该数据集进行的初步生物信息学分析确定了 BRAF V600E-LEAT 和对照之间的 2134 个差异表达基因。此外，基因集富集分析为雌激素反应相关途径与 BRAF V600E-LEAT 患者致癫痫性之间的关联提供了新的见解。我们的数据集和研究结果将有助于理解 LEAT 引起的癫痫病理学和确定新的治疗靶点。