We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

中文翻译：

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对1,000例小儿高级别和弥漫性固有性脑桥神经胶质瘤的综合分子荟萃分析。

我们整理了来自157例未发表的小儿高级别神经胶质瘤和弥漫性桥脑神经胶质瘤的数据，以及20多个可公开获得的数据集，对1000多个病例进行了综合分析。我们确定了组蛋白突变亚组中的共分离突变，包括H3.3G34R / V中FBXW7的缺失，H3.3K27M中TOP3A重排和H3.1K27M中的BCOR突变。组蛋白野生型亚组通过更接近低级肿瘤的关键致癌事件或甲基化谱的存在而得到完善。基因组像差随年龄增长而增加，突显了婴儿群体在生物学和临床上都与众不同。在小部分肿瘤中发现了罕见的通路失调，进一步定义了疾病的分子多样性，