染色体外DNA：塑造癌症的进化动力学
Extrachromosomal DNA: shaping the evolutionary dynamics of cancer.
作者信息
Haughey Magnus, Noorani Imran, Swanton Charles, Mischel Paul S, Werner Benjamin
机构信息
Evolutionary Dynamics Group, Centre for Cancer Evolution, Barts Cancer Centre, Queen Mary University of London, London, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK; Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, UK.
出版信息
Trends Cancer. 2025 Jul 9. doi: 10.1016/j.trecan.2025.06.004.
Cancers are complex, diverse, and elusive, with extrachromosomal DNA (ecDNA) recently emerging as a crucial player in driving the evolution of about 20% of all tumors. In this review we discuss open questions concerning the evolutionary role of ecDNA in tumor development, including tumorigenesis and metastatic seeding, the mutational landscape on ecDNA, the dynamic ecDNA genotype-phenotype map, the structural evolution of ecDNA, and how knowledge of tissue-specific ecDNA evolutionary paths can be leveraged to deliver more effective clinical treatment. Looking forward, evolutionary theoretical modeling will be instrumental in advancing new research in the field, and we explore how modeling has contributed to our understanding of the evolutionary principles governing ecDNA dynamics. Ultimately, these challenges must be tackled to improve clinical stratification and create tumor- and patient-specific ecDNA-based therapies.
癌症复杂多样且难以捉摸，其中染色体外DNA（ecDNA）最近成为推动约20%的所有肿瘤进化的关键因素。在这篇综述中，我们讨论了有关ecDNA在肿瘤发展中的进化作用的开放性问题，包括肿瘤发生和转移播种、ecDNA上的突变景观、动态ecDNA基因型-表型图谱、ecDNA的结构进化，以及如何利用组织特异性ecDNA进化路径的知识来提供更有效的临床治疗。展望未来，进化理论建模将有助于推动该领域的新研究，我们探讨了建模如何有助于我们理解控制ecDNA动态的进化原理。最终，必须应对这些挑战，以改善临床分层并创建基于肿瘤和患者特异性ecDNA的疗法。
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