Németh Eszter, DeWeerd Rachel A, Green Abby M, Szüts Dávid
Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States; Center for Genome Integrity, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States.
Methods Enzymol. 2025;713:101-114. doi: 10.1016/bs.mie.2024.12.003. Epub 2025 Mar 18.
Somatic mutations drive cancer initiation and tumor evolution. Therefore, the etiology of mutagenesis in cancer is important to preventative and treatment strategies. Somatic mutagenesis in cancer is a multifactorial process and includes both endogenous and exogenous sources of mutations. One recently recognized source of mutagenesis in cancer is the innate immune APOBEC3 family of enzymes, which catalyze cytosine deamination to restrict viral infection but can aberrantly act on the cellular genome, resulting in mutations. Single base substitution (SBS) signatures, or mutational patterns, identified in cancer genomes have demonstrated widespread mutagenesis caused by APOBEC3 enzymes throughout human tumors. To comprehensively define the consequences of APOBEC3 mutagenesis, we developed an experimental pipeline for prospective analysis of genome-wide mutations caused by APOBEC3 activity. This pipeline can be adapted to analyze additional sources of mutagenesis across a spectrum of cells.
体细胞突变驱动癌症的发生和肿瘤的演变。因此，癌症中诱变的病因对于预防和治疗策略很重要。癌症中的体细胞诱变是一个多因素过程，包括内源性和外源性突变来源。癌症中一种最近被认识到的诱变来源是先天免疫APOBEC3酶家族，其催化胞嘧啶脱氨以限制病毒感染，但可异常作用于细胞基因组，导致突变。在癌症基因组中鉴定出的单碱基替换（SBS）特征或突变模式已证明，APOBEC3酶在整个人类肿瘤中引起了广泛的诱变。为了全面定义APOBEC3诱变的后果，我们开发了一种实验流程，用于前瞻性分析由APOBEC3活性引起的全基因组突变。该流程可适用于分析一系列细胞中诱变的其他来源。
