The genome as a record of environmental exposure

TLDR

Whole‑genome sequencing of human tumours has uncovered distinct mutation patterns that suggest causative origins of cancer, yet studies of environmental mutagen‑induced mutation spectra have traditionally focused on single genes. The study aims to evaluate whole‑genome mutation spectra in experimental models using affordable sequencing platforms. The authors examined whole‑genome mutation profiles of mouse embryo fibroblasts immortalised after exposure to benzo[a]pyrene, ultraviolet light, and aristolochic acid. Each mutagen produced a distinct signature—G→T for BaP, C→T/CC→TT for UV, and A→T for AA—confirming known patterns, providing higher‑order genomic insights, and suggesting the method could identify mutagenic agents in human tumours and clarify cancer aetiology.

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.