Mutational spectra and mutational signatures: Insights into cancer aetiology and mechanisms of DNA damage and repair

DNA Repair
David H Phillips

Abstract

Reporter gene assays, in which a single mutation from each experiment can contribute to the assembly of a mutation spectrum for an agent, have provided the basis for understanding the mutational processes induced by mutagenic agents and for providing clues to the origins of mutations in human tumours. More recently exome and whole genome sequencing of human tumours has revealed distinct patterns of mutation that could provide additional clues for the causative origins of cancer. This can be tested by examining the mutational signatures induced in experimental systems by putative cancer-causing agents. Such signatures are now being generated in vitro in a number of different mutagen-exposed cellular systems. Results reveal that mutagens induce characteristic mutation signatures that, in some cases, match signatures found in human tumours. Proof of principle has been established with mutational signatures generated by simulated sunlight and aristolochic acid, which match those signatures found in human melanomas and urothelial cancers, respectively. In an analysis of somatic mutations in cancers for which tobacco smoking confers an elevated risk, it was found that smoking is associated with increased mutation burdens of multiple ...Continue Reading

Citations

Oct 11, 2019·Environmental Microbiology·Thomas Ferenci
Oct 9, 2019·Environmental and Molecular Mutagenesis·Jesse J Salk, Scott R Kennedy
Dec 4, 2019·Environmental and Molecular Mutagenesis·Philip Hanawalt, Joann Sweasy
Feb 16, 2020·Genome Biology·Gene KohSerena Nik-Zainal
Sep 25, 2020·Chemical Society Reviews·Cécile MingardShana J Sturla
Oct 9, 2019·Nature Communications·Sharon ChristensenArne Van Hoeck
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Jul 31, 2020·G3 : Genes - Genomes - Genetics·Ajith V PankajamKoodali T Nishant
Aug 12, 2020·Nature Reviews. Cancer·Francisco Martínez-JiménezNuria Lopez-Bigas
Feb 11, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Miriam C PoirierJohn Pierce Wise
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Oct 6, 2020·NAR Cancer·Xiaoju HuSubhajyoti De
Mar 14, 2021·American Journal of Epidemiology·Maria Teresa LandiStephen J Chanock
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Aug 31, 2021·Mutation Research·Min ZhangBarry Gold

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Methods Mentioned

BETA
PCR
transgenic
deamination
exome sequencing

Software Mentioned

TC
COSMIC
NER

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