EGFRvIII突变是胶质瘤诊断分型、预后判断和靶向治疗的重要标志物。申请人团队前期对转录组学和蛋白组学分析时发现，EGFRvIII突变能够激活WNT/β-catenin信号通路，调控组蛋白H2B翻译后修饰，进而促进肿瘤细胞间质转化及恶性生物学行为。在此基础上，本研究拟利用免疫沉淀等技术研究EGFRvIII/β-catenin引起H2BK15乙酰化及间质相关标志物上调的分子机制；明确EGFRvIII/miR-135b/MST1参与的H2BS14磷酸化及抑制凋亡的调控模式；进一步分析上述分子网络的增强机制及组蛋白调控之间的相互作用；使用布罗莫结构域抑制剂观察靶向组蛋白修饰对EGFRvIII突变胶质瘤的抑制作用。本研究可揭示EGFRvIII对脑胶质瘤中组蛋白翻译后修饰及其下游因子调控网络的影响，有望为胶质瘤临床标记物发现及个体化治疗提供理论基础。

EGFRvIII mutation is an important biomarker for glioma diagnosis, prognosis and targeted therapy. Our preliminary analyses of transcriptomic and proteomic data demonstrated that the EGFRvIII mutation could activate the WNT/β-catenin signaling pathway, regulate the post-translational modification of histone, and promote mesenchymal transition and malignancy in gliomas. Based on these results, we aim to investigate the molecular mechanism of EGFRvIII/β-catenin in H2BK15 acetylation and mesenchymal transition. We will clarify the functional implications of EGFRvIII/miR-135b/MST1 in H2BS14 phosphorylation and apoptosis resistance. Further experiments will be conducted to analyze the interactions among the EGFRvIII regulated molecular network and the interaction between histone modifications. Finally, we will use the antagonists of bromodomain to assess the inhibitory effect of targeted histone modification on EGFRvIII mutant glioma. This study will aid in revealing the effect of EGFRvIII on histone post-translational modification and its downstream regulation network in glioma, which is expected to provide a theoretical basis for clinical marker's discovery and tailored therapies of glioma.