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

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.

SUBMITTER: Riva L

PROVIDER: S-EPMC7610456 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Riva Laura L Pandiri Arun R AR Li Yun Rose YR Droop Alastair A Hewinson James J Quail Michael A MA Iyer Vivek V Shepherd Rebecca R Herbert Ronald A RA Campbell Peter J PJ Sills Robert C RC Alexandrov Ludmil B LB Balmain Allan A Adams David J DJ

Nature genetics 20200928 11

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 c ...[more]

PMID: 32989322

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Dataset Information

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

Publications

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

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