Background/Objectives: Lower-grade gliomas, particularlyIDH-mutant astrocytomas, represent a distinct molecular subtype with unique therapeutic challenges. Whole-genome sequencing (WGS) plays a crucial role in uncovering genetic alterations that drive glioma pathogenesis and therapeutic resistance. This study identifies and evaluates a novelGATA2p.Arg396Trp mutation in a clinical sample of lower-grade glioma, assessing its structural impact and implications for drug binding. Methods: A WHO Grade II astrocytoma specimen from a 33-year-old female patient was analyzed using WGS with Oxford Nanopore sequencing, followed by comprehensive bioinformatics processing to identify genomic variants. TheGATA2p.Arg396Trp mutation was evaluated using protein modeling, structural analysis, and pathogenicity prediction tools. Drug affinity analysis was conducted using molecular docking simulations to assess the computational impact of the mutation on drug binding. Results: TheGATA2p.Arg396Trp mutation was identified as a computationally predicted pathogenic variant, potentially disrupting protein interactions within critical functional domains. Structural analysis revealed altered binding dynamics with key anti-neoplastic agents, suggesting potential implications for therapeutic response. These findings represent computational predictions requiring experimental validation. Conclusions: Our preliminary findings suggest a potential role of theGATA2p.Arg396Trp mutation in lower-grade glioma pathogenesis. The mutation predicted impact on transcriptional regulation and drug affinity suggestsGATA2as a possible biomarker candidate. Extensive experimental validation in larger patient cohorts is needed to establish clinical relevance and explore targeted therapeutic strategies.
**背景/目的：** 低级别胶质瘤，特别是IDH突变型星形细胞瘤，代表了一种具有独特治疗挑战的分子亚型。全基因组测序在揭示驱动胶质瘤发病机制和治疗耐药的遗传改变方面起着至关重要的作用。本研究在一例低级别胶质瘤临床样本中鉴定并评估了一个新的GATA2 p.Arg396Trp突变，评估了其结构影响及对药物结合的意义。 **方法：** 对一例33岁女性患者的WHO II级星形细胞瘤样本，采用牛津纳米孔测序技术进行全基因组测序分析，随后通过全面的生物信息学处理以鉴定基因组变异。使用蛋白质建模、结构分析和致病性预测工具对GATA2 p.Arg396Trp突变进行评估。通过分子对接模拟进行药物亲和力分析，以评估该突变对药物结合的计算影响。 **结果：** GATA2 p.Arg396Trp突变被鉴定为一种计算预测的致病性变异，可能破坏关键功能域内的蛋白质相互作用。结构分析揭示了其与关键抗肿瘤药物的结合动力学发生改变，提示可能对治疗反应产生影响。这些发现属于计算预测，需要实验验证。 **结论：** 我们的初步研究结果表明，GATA2 p.Arg396Trp突变可能在低级别胶质瘤的发病机制中发挥作用。该突变对转录调控和药物亲和力的预测影响，提示GATA2可能成为一个潜在的生物标志物候选。需要在更大的患者队列中进行广泛的实验验证，以确立其临床相关性并探索靶向治疗策略。
肿瘤(癌症)患者之家