Some cancer therapies damage DNA and cause mutations in both cancerous and healthy cells. Therapy-induced mutations may underlie some of the long-term and late side effects of treatments, such as mental disabilities, organ toxicity and secondary neoplasms. Nevertheless, the burden of mutation contributed by different chemotherapies has not been explored. Here we identify the mutational signatures or footprints of six widely used anticancer therapies across more than 3,500 metastatic tumors originating from different organs. These include previously known and new mutational signatures generated by platinum-based drugs as well as a previously unknown signature of nucleoside metabolic inhibitors. Exploiting these mutational footprints, we estimate the contribution of different treatments to the mutation burden of tumors and their risk of contributing coding and potential driver mutations in the genome. The mutational footprints identified here allow for precise assessment of the mutational risk of different cancer therapies to understand their long-term side effects.

中文翻译：

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癌症治疗的突变足迹。

一些癌症疗法会破坏 DNA 并导致癌细胞和健康细胞发生突变。治疗诱导的突变可能是治疗的一些长期和晚期副作用的基础，例如精神残疾、器官毒性和继发性肿瘤。然而，尚未探索由不同化学疗法引起的突变负担。在这里，我们确定了来自不同器官的 3,500 多个转移性肿瘤中六种广泛使用的抗癌疗法的突变特征或足迹。这些包括以前已知的和新的由铂类药物产生的突变特征，以及以前未知的核苷代谢抑制剂特征。利用这些突变足迹，我们估计了不同治疗对肿瘤突变负担的贡献，以及它们在基因组中促成编码和潜在驱动突变的风险。此处确定的突变足迹允许精确评估不同癌症疗法的突变风险，以了解它们的长期副作用。