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Origin and initiation mechanisms of neuroblastoma

机译：神经母细胞瘤的起源和起始机制

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Neuroblastoma is an embryonal malignancy that affects normal development of the adrenal medulla and paravertebral sympathetic ganglia in early childhood. Extensive studies have revealed the molecular characteristics of human neuroblastomas, including abnormalities at genome, epigenome and transcriptome levels. However, neuroblastoma initiation mechanisms and even its origin are long-standing mysteries. In this review article, we summarize the current knowledge about normal development of putative neuroblastoma sources, namely sympathoadrenal lineage of neural crest cells and Schwann cell precursors that were recently identified as the source of adrenal chromaffin cells. A plausible origin of enigmatic stage 4S neuroblastoma is also discussed. With regard to the initiation mechanisms, we review genetic abnormalities in neuroblastomas and their possible association to initiation mechanisms. We also summarize evidences of neuroblastoma initiation observed in genetically engineered animal models, in which epigenetic alterations were involved, including transcriptomic upregulation by N-Myc and downregulation by polycomb repressive complex 2. Finally, several in vitro experimental methods are proposed that hopefully will accelerate our comprehension of neuroblastoma initiation. Thus, this review summarizes the state-of-the-art knowledge about the mechanisms of neuroblastoma initiation, which is critical for developing new strategies to cure children with neuroblastoma.
机译：神经母细胞瘤是一种胚胎恶性肿瘤，影响肾上腺髓质和椎间露髓质和椎旁同情神经节的正常发育。广泛的研究揭示了人类神经细胞瘤的分子特征，包括基因组，外形组和转录组水平的异常。然而，神经母细胞瘤引发机制甚至其起源是长期的奥秘。在本文中，我们总结了关于推定神经母细胞瘤源的正常发展的本知识，即最近被鉴定为肾上腺铬细胞来源的神经嵴细胞和施万细胞前体的同情谱系。还讨论了神秘阶段4S神经母细胞瘤的合理起源。关于启动机制，我们审查神经细胞母细胞瘤中的遗传异常及其与起始机制的可能结合。我们还总结了在遗传工程动物模型中观察到的神经母细胞瘤开始的证据，其中涉及表观遗传改变，包括通过N-Myc的转录组上调和通过Polycomb抑制复合物的下调。最后，提出了几种体外实验方法，希望能够加速我们的体外实验方法理解神经母细胞瘤的启动。因此，本综述总结了关于神经母细胞瘤引发机制的最先进的知识，这对于开发治疗神经母细胞瘤的新策略至关重要。

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