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The mutational footprints of cancer therapies

Oriol Pich, Ferran Muiños, Martijn Paul Lolkema, Neeltje Steeghs, Abel Gonzalez-Perez, Nuria Lopez-Bigas
doi: https://doi.org/10.1101/683268
Oriol Pich
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
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Ferran Muiños
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
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Martijn Paul Lolkema
2University Medical Center Utrecht, Heidelberglaan 100. 3584 CX Utrecht, The Netherlands
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Neeltje Steeghs
3The Netherlands Cancer Institute. Plesmanlaan 121 1066 CX Amsterdam The Netherlands
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Abel Gonzalez-Perez
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
4Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
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Nuria Lopez-Bigas
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
4Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
5Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
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  • For correspondence: nuria.lopez@irbbarcelona.org
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 27, 2019.
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The mutational footprints of cancer therapies
Oriol Pich, Ferran Muiños, Martijn Paul Lolkema, Neeltje Steeghs, Abel Gonzalez-Perez, Nuria Lopez-Bigas
bioRxiv 683268; doi: https://doi.org/10.1101/683268
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The mutational footprints of cancer therapies
Oriol Pich, Ferran Muiños, Martijn Paul Lolkema, Neeltje Steeghs, Abel Gonzalez-Perez, Nuria Lopez-Bigas
bioRxiv 683268; doi: https://doi.org/10.1101/683268

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