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The genome as a record of environmental exposure

Research output: Contribution to journalArticle

Serena Nik-Zainal, Jill E Kucab, Sandro Morganella, Dominik Glodzik, Ludmil B Alexandrov, Volker M Arlt, Annette Weninger, Monica Hollstein, Michael R Stratton, David H Phillips

Original languageEnglish
Pages (from-to)763-770
Number of pages8
JournalMutagenesis
Volume30
Issue number6
Early online date6 Oct 2015
DOIs
Publication statusPublished - Nov 2015

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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.

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