Department of Microbiology & Immunology, W. R. Hearst Microbiology Research Center, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
J Hematol Oncol. 2022 Aug 27;15(1):117. doi: 10.1186/s13045-022-01337-w.
A cardinal feature that distinguishes clinically high-risk neuroblastoma from low-risk tumors is telomere maintenance. Specifically, neuroblastoma tumors with either active telomerase or alternative lengthening of telomeres exhibit aggressive growth characteristics that lead to poor outcomes, whereas tumors without telomere maintenance can be managed with observation or minimal treatment. Even though the need for cancer cells to maintain telomere DNA-in order to sustain cell proliferation-is well established, recent studies suggest that the neural crest origin of neuroblastoma may enforce unique relationships between telomeres and tumor malignancy. Specifically in neuroblastoma, telomere structure and telomerase activity are correlated with the adrenergic/mesenchymal differentiation states, and manipulating telomerase activity can trigger tumor cell differentiation. Both findings may reflect features of normal neural crest development. This review summarizes recent advances in the characterization of telomere structure and telomere maintenance mechanisms in neuroblastoma and discusses the findings in the context of relevant literature on telomeres during embryonic and neural development. Understanding the canonical and non-canonical roles of telomere maintenance in neuroblastoma could reveal vulnerabilities for telomere-directed therapies with potential applications to other pediatric malignancies.
一个区分临床高危神经母细胞瘤与低危肿瘤的关键特征是端粒维持。具体来说，具有活性端粒酶或端粒的替代性延长的神经母细胞瘤肿瘤表现出侵袭性生长特征，导致不良结局，而没有端粒维持的肿瘤可以通过观察或最小化治疗来管理。尽管癌细胞需要维持端粒 DNA 以维持细胞增殖是明确的，但最近的研究表明，神经母细胞瘤的神经嵴起源可能在端粒和肿瘤恶性之间施加独特的关系。具体在神经母细胞瘤中，端粒结构和端粒酶活性与肾上腺素能/间充质分化状态相关，并且操纵端粒酶活性可以触发肿瘤细胞分化。这两个发现都可能反映了正常神经嵴发育的特征。这篇综述总结了神经母细胞瘤中端粒结构和端粒维持机制的特征描述方面的最新进展，并讨论了在胚胎和神经发育过程中端粒相关文献背景下的发现。了解端粒维持在神经母细胞瘤中的规范和非规范作用可能揭示针对端粒的治疗方法的脆弱性，这些方法可能适用于其他儿科恶性肿瘤。
