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解析进化背景下肿瘤发生的驱动因素:理论模型和生物信息学工具。

Unraveling the Drivers of Tumorigenesis in the Context of Evolution: Theoretical Models and Bioinformatics Tools.

机构信息

Innovation Institute for Artificial Intelligence in Medicine, Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, China.

出版信息

J Mol Evol. 2023 Aug;91(4):405-423. doi: 10.1007/s00239-023-10117-0. Epub 2023 May 29.

Abstract

Cancer originates from somatic cells that have accumulated mutations. These mutations alter the phenotype of the cells, allowing them to escape homeostatic regulation that maintains normal cell numbers. The emergence of malignancies is an evolutionary process in which the random accumulation of somatic mutations and sequential selection of dominant clones cause cancer cells to proliferate. The development of technologies such as high-throughput sequencing has provided a powerful means to measure subclonal evolutionary dynamics across space and time. Here, we review the patterns that may be observed in cancer evolution and the methods available for quantifying the evolutionary dynamics of cancer. An improved understanding of the evolutionary trajectories of cancer will enable us to explore the molecular mechanism of tumorigenesis and to design tailored treatment strategies.

摘要

癌症起源于积累了突变的体细胞。这些突变改变了细胞的表型,使它们能够逃脱维持正常细胞数量的体内平衡调节。恶性肿瘤的出现是一个进化过程,其中体细胞突变的随机积累和优势克隆的连续选择导致癌细胞增殖。高通量测序等技术的发展为跨越时空测量亚克隆进化动态提供了有力手段。在这里,我们回顾了可能在癌症进化中观察到的模式以及量化癌症进化动态的可用方法。对癌症进化轨迹的深入了解将使我们能够探索肿瘤发生的分子机制,并设计针对性的治疗策略。

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