文章：

表观基因组异质性作为肿瘤进化的一个来源

Epigenomic heterogeneity as a source of tumour evolution

原文发布日期：2024-10-16

DOI: 10.1038/s41568-024-00757-9

类型: Review Article

开放获取: 否

英文摘要：

In the past decade, remarkable progress in cancer medicine has been achieved by the development of treatments that target DNA sequence variants. However, a purely genetic approach to treatment selection is hampered by the fact that diverse cell states can emerge from the same genotype. In multicellular organisms, cell-state heterogeneity is driven by epigenetic processes that regulate DNA-based functions such as transcription; disruption of these processes is a hallmark of cancer that enables the emergence of defective cell states. Advances in single-cell technologies have unlocked our ability to quantify the epigenomic heterogeneity of tumours and understand its mechanisms, thereby transforming our appreciation of how epigenomic changes drive cancer evolution. This Review explores the idea that epigenomic heterogeneity and plasticity act as a reservoir of cell states and therefore as a source of tumour evolution. Best practices to quantify epigenomic heterogeneity and explore its various causes and consequences are discussed, including epigenomic reprogramming, stochastic changes and lasting memory. The design of new therapeutic approaches to restrict epigenomic heterogeneity, with the long-term objective of limiting cancer development and progression, is also addressed.

摘要翻译： 

过去十年间，针对DNA序列变异的治疗方法取得了显著进展，推动癌症医学实现重大突破。然而，单纯基于遗传学的治疗策略受到同一基因型可产生不同细胞状态的制约。在多细胞生物中，细胞状态异质性受表观遗传过程驱动，这些过程调控着转录等DNA功能，而其紊乱正是癌症的特征之一，促使异常细胞状态的形成。单细胞技术的进步使我们能够量化肿瘤的表观基因组异质性并解析其机制，从而改变了对表观基因组变化驱动癌症演化的认知。本综述探讨了表观基因组异质性与可塑性作为细胞状态储备库进而推动肿瘤演化的观点，阐述了量化表观基因组异质性的最佳实践，分析了其多种成因与后果（包括表观遗传重编程、随机变化和持久记忆），并提出了限制表观基因组异质性的新型治疗策略，其长期目标在于抑制癌症的发生与发展。

原文链接：

Epigenomic heterogeneity as a source of tumour evolution