PT  - JOURNAL ARTICLE
AU  - Pich, Oriol
AU  - Muiños, Ferran
AU  - Lolkema, Martijn Paul
AU  - Steeghs, Neeltje
AU  - Gonzalez-Perez, Abel
AU  - Lopez-Bigas, Nuria
TI  - The mutational footprints of cancer therapies
AID  - 10.1101/683268
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 683268
4099  - http://biorxiv.org/content/early/2019/06/27/683268.short
4100  - http://biorxiv.org/content/early/2019/06/27/683268.full
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.