Mutational Signatures in Cancer Genomics and Toxicology

Genomic instability, a hallmark of cancer, manifests through the accumulation of somatic mutations arising from various endogenous and exogenous processes. High-throughput sequencing of cancer genomes has revealed distinct mutational patterns, termed mutational signatures, that reflect the individual underlying mutagenic processes operative during carcinogenesis. These signatures provide insights into the etiology of cancer-associated mutations. To validate the proposed etiologies and elucidate the complex mutational landscapes observed in human cancers, robust experimental systems are essential. Here, we describe a multi-model approach to deciphering mutational signatures, employing mammalian cell lines, chicken cells, rodent carcinogenesis models, and the nematode C. elegans. These diverse systems enable the systematic investigation of exogenous mutagen-induced signatures, elucidating species-specific responses to genotoxic agents.