Center for Genomic Integrity, Institute for Basic Science, Ulsan, Republic of Korea.
Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Biochem Soc Trans. 2023 Jun 28;51(3):1307-1317. doi: 10.1042/BST20221482.
Cells constantly accumulate mutations, which are caused by replication errors, as well as through the action of endogenous and exogenous DNA-damaging agents. Mutational patterns reflect the status of DNA repair machinery and the history of genotoxin exposure of a given cellular clone. Computationally derived mutational signatures can shed light on the origins of cancer. However, to understand the etiology of cancer signatures, they need to be compared with experimental signatures, which are obtained from the isogenic cell lines or organisms under controlled conditions. Experimental mutational patterns were instrumental in understanding the nature of signatures caused by mismatch repair and BRCA deficiencies. Here, we describe how different cell lines and model organisms were used in recent years to decipher mutational signatures observed in cancer genomes and provide examples of how data from different experimental systems complement and support each other.
细胞不断积累突变，这些突变是由复制错误以及内源性和外源性 DNA 损伤剂的作用引起的。突变模式反映了 DNA 修复机制的状态以及特定细胞克隆的遗传毒物暴露史。通过计算推导出来的突变特征可以揭示癌症的起源。然而，为了了解癌症特征的病因，需要将它们与实验特征进行比较，这些实验特征是从同基因细胞系或在受控条件下的生物体中获得的。实验性的突变模式对于理解由错配修复和 BRCA 缺陷引起的特征的性质具有重要意义。在这里，我们描述了近年来如何使用不同的细胞系和模式生物来破译在癌症基因组中观察到的突变特征，并提供了一些例子，说明来自不同实验系统的数据如何相互补充和支持。
