RT Journal Article SR Electronic T1 The mutational footprints of cancer therapies JF bioRxiv FD Cold Spring Harbor Laboratory SP 683268 DO 10.1101/683268 A1 Pich, Oriol A1 MuiƱos, Ferran A1 Lolkema, Martijn Paul A1 Steeghs, Neeltje A1 Gonzalez-Perez, Abel A1 Lopez-Bigas, Nuria YR 2019 UL http://biorxiv.org/content/early/2019/06/27/683268.abstract AB Some cancer therapies damage DNA and cause mutations both in cancer and healthy cells of the patient1. These therapy-induced mutations may underlie some of the long-term and late side effects of the treatment, such as mental disabilities, organ toxicities and secondary neoplasms. Currently we ignore the mutation pattern and burden caused by different cancer treatments. Here we identify mutational signatures, or footprints of six widely-used anti-cancer therapies with the study of whole-genomes from more than 3500 metastatic tumors originated in different organs. These include previously known and new mutational signatures generated by platinum-based drugs, and a novel signature of treatment with nucleoside metabolic inhibitors. Exploiting these mutational footprints, we estimate the contribution of different treatments to the mutation burden of tumors and their risk of causing coding and likely driver mutations in the genome. In summary, the mutational footprints identified here open a window to precisely appraise the mutational risk of different cancer therapies to understand their late side effects.