Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either by mechanisms that activateTERTor through the alternative lengthening of telomeres pathway. Neuroblastoma is a heterogeneous pediatric cancer, and the aim of this study was to characterize telomere maintenance mechanisms in a high-risk neuroblastoma cohort. All tumor samples were profiled with SNP microarrays and, when material was available, subjected to whole genome sequencing (WGS). Telomere length was estimated from WGS data, samples were assayed for the ALT biomarker c-circles, and selected samples were subjected to methylation array analysis. Samples withATRXaberration in this study were positive for c-circles, whereas samples with eitherMYCNamplification orTERTre-arrangement were negative for c-circles. BothATRXaberrations andTERTre-arrangement were enriched in 11q-deleted samples. An association between older age at diagnosis and 1q-deletion was found in the ALT-positive group.TERTwas frequently placed in juxtaposition to a previously established gene in neuroblastoma tumorigenesis or cancer in general. Given the importance of high-risk neuroblastoma, means for mitigating active telomere maintenance must be therapeutically explored.
肿瘤细胞的特征在于其能够进行无限次细胞分裂，这通常通过激活TERT的机制或通过端粒替代延长途径实现。神经母细胞瘤是一种异质性儿童癌症，本研究旨在描述高危神经母细胞瘤队列中的端粒维持机制。所有肿瘤样本均采用SNP微阵列进行分析，并在材料可用时进行全基因组测序。端粒长度通过WGS数据估算，样本检测了ALT生物标志物c-circles，并对选定样本进行了甲基化阵列分析。本研究中存在ATRX异常的样本c-circles检测呈阳性，而具有MYCN扩增或TERT重排的样本c-circles检测呈阴性。ATRX异常和TERT重排在11q缺失样本中均呈现富集现象。在ALT阳性组中发现诊断年龄较大与1q缺失存在关联。TERT常与神经母细胞瘤发生或癌症中先前已确认的基因并置。鉴于高危神经母细胞瘤的重要性，必须在治疗层面探索抑制活性端粒维持机制的方法。
肿瘤(癌症)患者之家