表观基因组异质性作为肿瘤演化的来源
Epigenomic heterogeneity as a source of tumour evolution
DOI 原文链接
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影响因子:66.8
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
DOI:
10.1038/s41568-024-00757-9
摘要
在过去十年，通过靶向DNA序列变异的治疗方法取得了显著的癌症医学进展。然而，单纯的遗传方法在治疗选择上受到限制，因为不同的细胞状态可以由相同的基因型引发。在多细胞生物中，细胞状态异质性由调控DNA功能如转录的表观遗传过程驱动；这些过程的破坏是癌症的标志之一，促使异常细胞状态的出现。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及其机制，从而改变了我们对表观基因组变化驱动癌症演化的理解。本文探讨了表观基因组异质性和可塑性作为细胞状态的储库和肿瘤演化源的观点。讨论了量化表观基因组异质性的方法，包括表观基因组重编程、随机变化和持久记忆，旨在设计新型治疗策略，以限制表观基因组异质性，最终目标是抑制癌症的发展和进展。
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.