表观基因组异质性作为肿瘤进化的来源
Epigenomic heterogeneity as a source of tumour evolution
影响因子:66.80000
分区:医学1区 Top / 肿瘤学1区
发表日期:2025 Jan
作者:
Marthe Laisné, Mathieu Lupien, Céline Vallot
摘要
在过去的十年中，通过靶向DNA序列变异的治疗方法，已经取得了显着的癌症医学进展。但是，纯粹的遗传方法可以通过从相同的基因型中出现不同的细胞状态来阻碍这样的事实。在多细胞生物中，细胞态异质性是由调节基于DNA的功能（例如转录）的表观遗传过程驱动的。这些过程的破坏是癌症的标志，它使细胞状态有缺陷。单细胞技术的进步已解锁了我们量化肿瘤表观异质性异质性并了解其机制的能力，从而改变了我们对表观基因组变化如何促进癌症进化的欣赏。这篇综述探讨了表观基因组异质性和可塑性充当细胞态的储层，因此是肿瘤进化的来源。讨论了量化表观基因组异质性并探索其各种原因和后果的最佳实践，包括表观基因组重编程，随机变化和持久记忆。还解决了限制表观基因组异质性的新治疗方法的设计，以限制癌症发展和进展的长期目标。
Abstract
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.