Table 1 Mutational signatures assigned to IARC Group 1 carcinogen exposures

Name	Exposure	Group 1 carcinogen	Chemical class	Characteristic pre-mutagenic DNA lesion	Signature hallmarks	Prominent trinucleotide target in the signature
Signature 4	Tobacco smoke	Benzo[a]pyrene	PAH	(+)benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-dG adduct	G to T GG to TT tandem mutations Transcriptional strand bias	GGGGGA
Signature 7	Sunlight	Ultraviolet light	NA	Py-Py photodimers	C to T at dipyrimidines CC to TT tandem mutations Transcriptional strand bias	TCC
Signature 11	Chemotherapy	Temozolomide	Alkylating agent	O⁶-methylguanine	G to A Transcriptional strand bias	GGGGGA
Signature 22	Dietary contaminant (grain); herbal medicine	Aristolochic acid	Plant alkaloid	7-(deoxyadenosin-N(6)-yl) aristolactam I adduct	A to T Transcriptional strand bias	CAG
Signature 24	Dietary contaminant (groundnuts)	Aflatoxins	Fungal toxin	8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B₁ adduct	G to T Transcriptional strand bias	GGC
Signature 29	Tobacco chewing	Unspecified	Unspecified	Unspecified	G to T Transcriptional strand bias	TGCGGCTGT

Abbreviations: IARC, International Agency for Research on Cancer; NA, not applicable; PAH, polycyclic aromatic hydrocarbon; Py, pyrimidine.
Group 1 refers to the IARC classification of substances for which there is sufficient evidence of carcinogenicity to humans. The third column lists sources of exposure with documented links to cancer risk. Bases and context sequence are shown to reflect the base targeted by the mutagen (for example, as 5′-GGA-3′ for B[a]P, but as 5′-TCC-3′ for UV). The targeted base in its preferred sequence context is underlined in the last column. The targeted trinucleotides in the last column are extracted from signature analysis of human tumours; analysis of experimental models with single, controlled exposures recapitulates major features from the human data (Figure 2).

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