Abstract：
Pediatric high-grade gliomas represent a heterogeneous group of tumors with a wide variety of molecular features. We performed whole exome sequencing and methylation profiling on matched primary and recurrent tumors from four pediatric patients with hemispheric high-grade gliomas. Genetic analysis showed the presence of some variants shared between primary and recurrent tumors, along with other variants exclusive of primary or recurrent tumors. NSD1 variants, all novel and not previously reported, were present at high frequency in our series (100%) and were all shared between the samples, independently of primary or recurrence. For every variant, in silico prediction tools estimated a high probability of altering protein function. The novel NSD1 variant (c.5924T > A; p.Leu1975His) was present in one in four cases at recurrence, and in two in four cases at primary. The novel NSD1 variant (c.5993T > A; p.Met1998Lys) was present in one in four cases both at primary and recurrence, and in one in four cases only at primary. The presence of NSD1 mutations only at recurrence may suggest that they can be sub-clonal, while the presence in both primary and recurrence implies that they can also represent early and stable events. Furthermore, their presence only in primary, but not in recurrent tumors, suggest that NSD1 mutations may also be influenced by treatment.
摘要：
小儿高级别神经胶质瘤代表一组具有多种分子特征的异质性肿瘤。我们对四名患有半球高级别神经胶质瘤的儿科患者的匹配的原发性和复发性肿瘤进行了全外显子组测序和甲基化分析。遗传分析显示，原发性和复发性肿瘤之间存在一些共有的变异，以及除原发性或复发性肿瘤外的其他变体。NSD1变体，都是小说，以前没有报道过，在我们的系列中出现频率很高(100%)，并且都在样本之间共享，独立于原发或复发。对于每个变体，计算机预测工具估计改变蛋白质功能的可能性很高。新的NSD1变体（c.5924T＆gt;A;p.Leu1975His）在复发的四分之一病例中存在，在小学的四个案例中，有两个。新的NSD1变体（c.5993T＆gt;A;p.Met1998Lys）在原发和复发的情况下都出现在四分之一的病例中，只有四分之一的人在小学。NSD1突变仅在复发时的存在可能表明它们可能是亚克隆的，而在原发和复发中的存在意味着它们也可以代表早期和稳定的事件。此外，他们只在小学出现，但不是复发性肿瘤，提示NSD1突变也可能受到治疗的影响。
