The genome as a record of environmental exposure.
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Authors
Nik-Zainal, Serena
Kucab, Jill E
Morganella, Sandro
Glodzik, Dominik
Alexandrov, Ludmil B
Arlt, Volker M
Weninger, Annette
Hollstein, Monica
Stratton, Michael R
Phillips, David H
Publication Date
2015-11Journal Title
Mutagenesis
ISSN
0267-8357
Publisher
Oxford University Press (OUP)
Volume
30
Issue
6
Pages
763-770
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Nik-Zainal, S., Kucab, J. E., Morganella, S., Glodzik, D., Alexandrov, L. B., Arlt, V. M., Weninger, A., et al. (2015). The genome as a record of environmental exposure.. Mutagenesis, 30 (6), 763-770. https://doi.org/10.1093/mutage/gev073
Abstract
Whole genome sequencing of human tumours has revealed distinct patterns of mutation that hint at the causative origins of cancer. Experimental investigations of the mutations and mutation spectra induced by environmental mutagens have traditionally focused on single genes. With the advent of faster cheaper sequencing platforms, it is now possible to assess mutation spectra in experimental models across the whole genome. As a proof of principle, we have examined the whole genome mutation profiles of mouse embryo fibroblasts immortalised following exposure to benzo[a]pyrene (BaP), ultraviolet light (UV) and aristolochic acid (AA). The results reveal that each mutagen induces a characteristic mutation signature: predominantly G→T mutations for BaP, C→T and CC→TT for UV and A→T for AA. The data are not only consistent with existing knowledge but also provide additional information at higher levels of genomic organisation. The approach holds promise for identifying agents responsible for mutations in human tumours and for shedding light on the aetiology of human cancer.
Keywords
Animals, Cell Line, Cell Transformation, Neoplastic, DNA Mutational Analysis, DNA Replication, Environmental Exposure, Fibroblasts, Genome, Genome-Wide Association Study, Genomics, High-Throughput Nucleotide Sequencing, Humans, Mice, Mutagenesis, Mutagens, Mutation, Neoplasms, Transcription, Genetic
Sponsorship
Wellcome Trust (101126/Z/13/Z)
Identifiers
External DOI: https://doi.org/10.1093/mutage/gev073
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280056
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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