We performed genome-wide methylation analysis on 136 pediatric low-grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma-like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken-wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high-grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (>10 chromosomes altered), but none showed 1p/19q co-deletion or IDH1 p.R132H mutation. Hierarchical clustering and t-stochastic neighbor embedding analyses from DNA methylation data cluster them more closely to previously described pediatric-type low-grade gliomas and separate from adult gliomas. These tumors exhibit distinct clinical features; they are temporal lobe lesions occurring in adolescents and young adults with a prolonged history of seizures and all are alive with no recurrence (follow-up 3.2 to 13.2 years). We encountered another young adult case with quite similar pathological appearance and molecular status except for TERT promoter mutation. Although the series is small, these may represent a new category of IDH wild-type low-grade gliomas which may be confused with "molecular GBM." Further, they highlight the heterogeneity of IDH wild-type gliomas and the relatively indolent behavior of "pediatric-type" gliomas.

中文翻译：

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BRAF V600E 突变型少突胶质细胞瘤样肿瘤，在青少年和年轻成人中具有染色体不稳定性。

我们对 136 个小儿低级别胶质瘤进行了全基因组甲基化分析，确定了一个独特的簇，由三个具有少突胶质细胞瘤样组织学、BRAF p.V600E 突变和复发性全染色体增益 7 和丢失 10 的肿瘤组成。 形态学上，所有这些都显示类似的特征，包括由具有核周晕环的圆形核组成的弥漫性浸润性胶质瘤、分支毛细血管的鸡丝状图案和微钙化。没有一个显示星形细胞特征或特征提示高级别肿瘤，包括坏死或有丝分裂象。所有肿瘤都存在多个染色体拷贝数异常（> 10 条染色体改变），但没有一个显示 1p/19q 共缺失或 IDH1 p.R132H 突变。来自 DNA 甲基化数据的分层聚类和 t 随机邻居嵌入分析将它们更接近于先前描述的儿科型低级别神经胶质瘤，并与成人神经胶质瘤分开。这些肿瘤表现出不同的临床特征；它们是发生在具有长期癫痫病史的青少年和年轻成人中的颞叶病变，并且全部存活且未复发（随访 3.2 至 13.2 年）。除了 TERT 启动子突变外，我们遇到了另一个具有非常相似的病理外观和分子状态的年轻成人病例。虽然系列很小，但这些可能代表了 IDH 野生型低级别胶质瘤的新类别，可能与“分子 GBM”相混淆。此外，他们强调了 IDH 野生型胶质瘤的异质性和“