The mutational signature profile of known and suspected human carcinogens in mice
- 28 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 52 (11), 1189-1197
- https://doi.org/10.1038/s41588-020-0692-4
Abstract
Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from mice chronically exposed to 1 of 20 known or suspected human carcinogens, we reveal that most agents do not generate distinct mutational signatures or increase mutation burden, with most mutations, including driver mutations, resulting from tissue-specific endogenous processes. We identify signatures resulting from exposure to cobalt and vinylidene chloride and link distinct human signatures (SBS19 and SBS42) with 1,2,3-trichloropropane, a haloalkane and pollutant of drinking water, and find these and other signatures in human tumor genomes. We define the cross-species genomic landscape of tumors induced by an important compendium of agents with relevance to human health.Keywords
Funding Information
- Cancer Research UK (21717, 21717, 21717)
- U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences
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