Dissecting genetic and environmental mutation signatures with model organisms.
Deep sequencing has impacted on cancer research by enabling routine sequencing of genomes and exomes to identify genetic changes associated with carcinogenesis. Researchers can now use the frequency, type, and context of all mutations in tumor genomes to extract mutation signatures that reflect the driving mutational processes. Identifying mutation signatures, however, may not immediately suggest a mechanism. Consequently, several recent studies have employed deep sequencing of model organisms exposed to discrete genetic or environmental perturbations. These studies exploit the simpler genomes and availability of powerful genetic tools in model organisms to analyze mutation signatures under controlled conditions, forging mechanistic links between mutational processes and signatures. We discuss the power of this approach and suggest that many such studies may be on the horizon.
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z3, Canada.
Romulo
R
Segovia
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z3, Canada.
Annie S
AS
Tam
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z3, Canada.
Peter C
PC
Stirling
D000818:Animals; D004777:Environment; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D009369:Neoplasms / Q000235:genetics
cancer genomics; deep sequencing; model organisms; mutagens; mutation signature