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The genome as a record of environmental exposure.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Nik-Zainal, Serena 
Kucab, Jill E 
Morganella, Sandro 
Glodzik, Dominik 
Alexandrov, Ludmil B 

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.

Description

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

Journal Title

Mutagenesis

Conference Name

Journal ISSN

0267-8357
1464-3804

Volume Title

30

Publisher

Oxford University Press (OUP)
Sponsorship
Wellcome Trust (101126/Z/13/Z)