A majority of cancers (~85%) activate the enzyme telomerase to maintain telomere length over multiple rounds of cellular division. Telomerase-negative cancers activate a distinct, telomerase-independent mechanism of telomere maintenance termed Alternative lengthening of telomeres (ALT). ALT uses homologous recombination to maintain telomere length and exhibits features of break-induced DNA replication. In malignant gliomas, the activation of either telomerase or ALT is nearly ubiquitous in pediatric and adult tumors, and the frequency with which these distinct telomere maintenance mechanisms is activated varies according to genetically-defined glioma subtypes. In this review, we summarize the current state of the field of telomere maintenance mechanisms (TMMs) and their relevance to glioma biology and therapy. We review the genetic alterations and molecular mechanisms leading to telomerase activation or ALT induction in pediatric and adult gliomas. With this background, we review emerging evidence on strategies for targeting TMMs for glioma therapy. Finally, we comment on critical gaps and issues for moving the field forward to translate our improved understanding of glioma telomere maintenance into better therapeutic strategies for patients.

中文翻译：

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恶性神经胶质瘤的端粒维持机制和相关治疗脆弱性

大多数癌症（约 85%）会激活端粒酶，以在多轮细胞分裂中维持端粒长度。端粒酶阴性癌症激活一种独特的、不依赖于端粒酶的端粒维持机制，称为端粒替代性延长（ALT）。 ALT 使用同源重组来维持端粒长度并表现出断裂诱导的 DNA 复制的特征。在恶性神经胶质瘤中，端粒酶或 ALT 的激活在儿童和成人肿瘤中几乎普遍存在，并且这些不同的端粒维持机制被激活的频率根据基因定义的神经胶质瘤亚型而变化。在这篇综述中，我们总结了端粒维持机制（TMM）领域的现状及其与神经胶质瘤生物学和治疗的相关性。我们回顾了儿童和成人神经胶质瘤中导致端粒酶激活或 ALT 诱导的遗传改变和分子机制。在此背景下，我们回顾了有关针对神经胶质瘤治疗的 TMM 策略的新证据。最后，我们评论了推动该领域向前发展的关键差距和问题，以将我们对神经胶质瘤端粒维持的更好理解转化为更好的患者治疗策略。