The mutational signature profile of known and suspected human carcinogens in mice.

Nature genetics 2020 Nov

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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.

Citation

Laura Riva, Arun R Pandiri, Yun Rose Li, Alastair Droop, James Hewinson, Michael A Quail, Vivek Iyer, Rebecca Shepherd, Ronald A Herbert, Peter J Campbell, Robert C Sills, Ludmil B Alexandrov, Allan Balmain, David J Adams. The mutational signature profile of known and suspected human carcinogens in mice. Nature genetics. 2020 Nov;52(11):1189-1197