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Epigenetic regulation of neuroblastoma development

机译:神经母细胞瘤发展的表观遗传调节

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In recent years, technological advances have enabled a detailed landscaping of the epigenome and the mechanisms of epigenetic regulation that drive normal cell function, development and cancer. Rather than merely a structural entity to support genome compaction, we now look at chromatin as a very dynamic and essential constellation that is actively participating in the tight orchestration of transcriptional regulation as well as DNA replication and repair. The unique feature of chromatin flexibility enabling fast switches towards more or less restricted epigenetic cellular states is, not surprisingly, intimately connected to cancer development and treatment resistance, and the central role of epigenetic alterations in cancer is illustrated by the finding that up to 50% of all mutations across cancer entities affect proteins controlling the chromatin status. We summarize recent insights into epigenetic rewiring underlying neuroblastoma (NB) tumor formation ranging from changes in DNA methylation patterns and mutations in epigenetic regulators to global effects on transcriptional regulatory circuits that involve key players in NB oncogenesis. Insights into the disruption of the homeostatic epigenetic balance contributing to developmental arrest of sympathetic progenitor cells and subsequent NB oncogenesis are rapidly growing and will be exploited towards the development of novel therapeutic strategies to increase current survival rates of patients with high-risk NB.
机译:近年来,技术进步使得表述表观组织的详细景观和介绍正常细胞功能,发展和癌症的表观遗传调控机制。而不是仅仅是支持基因组压实的结构实体,我们现在将染色质视为一种非常动态和基本的星座,这是积极参与转录调节的紧密编队以及DNA复制和修复。染色质柔韧性的独特特征,使得快速切换到或多或少受限制的表观遗传细胞状态,并不令人惊讶地联系在癌症发育和治疗抵抗力,并且表观遗传改变在癌症中的核心作用是达到的,结果高达50%癌症实体的所有突变影响控制染色质状态的蛋白质。我们概述了最近对表观遗传重新挤出的潜在神经母细胞瘤(Nb)肿瘤形成的洞察力范围从表述调节剂中DNA甲基化模式和突变的变化到转录调节性电路的全局影响,这是涉及Nb蜂房中的关键参与者。洞察中断稳态表观遗传平衡导致同情祖细胞和随后的NB癌症的发育急剧丧生,并将迅速增长,并将利用新的治疗策略,以提高高风险Nb患者的当前存活率。

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