The genome as a record of environmental exposure

TY - JOUR

T1 - The genome as a record of environmental exposure

AU - Nik-Zainal, Serena

AU - Kucab, Jill E

AU - Morganella, Sandro

AU - Glodzik, Dominik

AU - Alexandrov, Ludmil B

AU - Arlt, Volker M

AU - Weninger, Annette

AU - Hollstein, Monica

AU - Stratton, Michael R

AU - Phillips, David H

N1 - © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.

PY - 2015/11

Y1 - 2015/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84983738682&partnerID=8YFLogxK

U2 - 10.1093/mutage/gev073

DO - 10.1093/mutage/gev073

M3 - Article

C2 - 26443852

SN - 0267-8357

VL - 30

SP - 763

EP - 770

JO - Mutagenesis

JF - Mutagenesis

IS - 6

ER -