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

Area of Science:

• Environmental health
• Genomics
• Cancer research

Background:

• Epidemiological studies link environmental agents to increased cancer risk.
• Understanding the genomic impact of carcinogen exposure is crucial for public health.

Purpose of the Study:

• To investigate the mutational landscape of tumors induced by various environmental carcinogens in mice.
• To identify specific mutational signatures associated with carcinogen exposure.
• To compare cross-species genomic alterations in tumors from exposed animals and humans.

Main Methods:

• Chronic exposure of mice to 20 known or suspected human carcinogens.
• Analysis of tumor genomes to identify mutations and mutational signatures.
• Comparison of mouse tumor genomic data with human tumor genomes.

Main Results:

• Most environmental agents did not generate distinct mutational signatures or increase overall mutation burden.
• Mutations, including driver mutations, predominantly resulted from tissue-specific endogenous processes.
• Identified signatures linked to cobalt and vinylidene chloride exposure.
• Linked human signatures (SBS19 and SBS42) to 1,2,3-trichloropropane exposure and found them in human tumors.

Conclusions:

• Carcinogen exposure has a limited impact on generating distinct mutational signatures.
• Endogenous processes are the primary drivers of mutations in cancer, even under carcinogen exposure.
• Specific mutational signatures can be linked to certain environmental agents, aiding in understanding human cancer etiology.