Lu Bingxin
School of Biosciences and Medicine, University of Surrey, Guildford GU2 7XH, UK.
Surrey Institute for People-Centred Artificial Intelligence, University of Surrey, Guildford GU2 7XH, UK.
Cancer Pathog Ther. 2024 Apr 18;3(1):16-29. doi: 10.1016/j.cpt.2024.04.003. eCollection 2025 Jan.
Cancer is an evolutionary process involving the accumulation of diverse somatic mutations and clonal evolution over time. Phylogenetic inference from samples obtained from an individual patient offers a powerful approach to unraveling the intricate evolutionary history of cancer and provides insights that can inform cancer treatment. Somatic copy number alterations (CNAs) are important in cancer evolution and are often used as markers, alone or with other somatic mutations, for phylogenetic inferences, particularly in low-coverage DNA sequencing data. Many phylogenetic inference methods using CNAs detected from bulk or single-cell DNA sequencing data have been developed over the years. However, there have been no systematic reviews on these methods. To summarize the state-of-the-art of the field and inform future development, this review presents a comprehensive survey on the major challenges in inference, different types of methods, and applications of these methods. The challenges are discussed from the aspects of input data, models of evolution, and inference algorithms. The different methods are grouped according to the markers used for inference and the types of the reconstructed trees. The applications include using phylogenetic inference to understand intra-tumor heterogeneity, metastasis, treatment resistance, and early cancer development. This review also sheds light on future directions of cancer phylogenetic inference using CNAs, including the improvement of scalability, the utilization of new types of data, and the development of more realistic models of evolution.
癌症是一个进化过程,涉及多种体细胞突变的积累以及随时间的克隆进化。从个体患者获取的样本进行系统发育推断,为揭示癌症复杂的进化史提供了一种强有力的方法,并能提供可为癌症治疗提供参考的见解。体细胞拷贝数改变(CNA)在癌症进化中很重要,常被单独或与其他体细胞突变一起用作系统发育推断的标记,尤其是在低覆盖度DNA测序数据中。多年来,已经开发了许多利用从批量或单细胞DNA测序数据中检测到的CNA的系统发育推断方法。然而,尚未对这些方法进行系统综述。为了总结该领域的最新进展并为未来发展提供参考,本综述对推断中的主要挑战、不同类型的方法以及这些方法的应用进行了全面调查。从输入数据、进化模型和推断算法等方面讨论了这些挑战。根据用于推断的标记和重建树的类型对不同方法进行了分组。应用包括利用系统发育推断来理解肿瘤内异质性、转移、治疗抗性和癌症早期发展。本综述还阐明了使用CNA进行癌症系统发育推断的未来方向,包括可扩展性的提高、新型数据的利用以及更现实进化模型的开发。