近日，西班牙巴塞罗那科学技术学院Nuria Lopez-Bigas及其小组绘制了肿瘤疗法引起的基因突变图谱。相关论文于2019年11月18日在线发表于《自然—遗传学》。

研究人员确定了六种广泛使用的抗癌疗法的突变特征或足迹，这些疗法广泛应用于源自不同器官的3500多种转移性肿瘤。这些包括基于铂的药物产生的已知和新的突变特征以及核苷代谢抑制剂的未知特征。利用这些突变足迹，研究人员估计了不同疗法对肿瘤突变负担的贡献及其在基因组中贡献编码和潜在驱动子突变的风险。这些确定的突变足迹可以精确评估不同癌症疗法的突变风险，以了解其长期副作用。

据介绍，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。治疗引起的突变可能是治疗的某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，目前的研究尚未探索由不同化学疗法引起的突变的负担。

附：英文原文

Title: The mutational footprints of cancer therapies

Author: Oriol Pich, Ferran Muios, Martijn Paul Lolkema, Neeltje Steeghs, Abel Gonzalez-Perez, Nuria Lopez-Bigas

Issue&Volume: 2019-11-18

Abstract: 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.

DOI: 10.1038/s41588-019-0525-5

Source: https://www.nature.com/articles/s41588-019-0525-5