Chen Zirong, Peng Peng, Zhang Xiaolin, Mania-Farnell Barbara, Xi Guifa, Wan Feng
Department of Neurological Surgery, Tongji Hospital, Tongji Medical College, Huazhong University Science and Technology, Wuhan 430030, China.
Department of Biological Science, Purdue University Northwest, Hammond, IN 46323, USA.
Cancers (Basel). 2021 Mar 5;13(5):1114. doi: 10.3390/cancers13051114.
Diffuse intrinsic pontine gliomas (DIPGs) account for ~15% of pediatric brain tumors, which invariably present with poor survival regardless of treatment mode. Several seminal studies have revealed that 80% of DIPGs harbor H3K27M mutation coded by , and genes. The H3K27M mutation has broad effects on gene expression and is considered a tumor driver. Determination of the effects of H3K27M on posttranslational histone modifications and gene regulations in DIPG is critical for identifying effective therapeutic targets. Advanced animal models play critical roles in translating these cutting-edge findings into clinical trial development. Here, we review current molecular research progress associated with DIPG. We also summarize DIPG animal models, highlighting novel genomic engineered mouse models (GEMMs) and innovative humanized DIPG mouse models. These models will pave the way towards personalized precision medicine for the treatment of DIPGs.
弥漫性脑桥内在型胶质瘤（DIPG）约占儿童脑肿瘤的15%，无论采用何种治疗方式，其生存率始终很低。多项开创性研究表明，80%的DIPG存在由、和基因编码的H3K27M突变。H3K27M突变对基因表达有广泛影响，被认为是肿瘤驱动因素。确定H3K27M对DIPG中组蛋白翻译后修饰和基因调控的影响对于识别有效的治疗靶点至关重要。先进的动物模型在将这些前沿发现转化为临床试验发展中起着关键作用。在此，我们综述了与DIPG相关的当前分子研究进展。我们还总结了DIPG动物模型，重点介绍了新型基因组工程小鼠模型（GEMM）和创新的人源化DIPG小鼠模型。这些模型将为DIPG的个性化精准治疗铺平道路。
