Figure 2

A carcinogen’s fingerprint in human tumour DNA can be reproduced in experimental systems. Mutation distribution spectra (showing frequency of base substitution type and context) from exome sequencing of primary human tumours, cells exposed in culture, or tumours of exposed mice. (a) Upper panels: spectra in upper urinary tract urothelial carcinomas (UTUC) of patients from Taiwan, China and from Balkan Endemic nephropathy (BEN) regions of Europe, two populations known to be exposed to AA.^{75, 76, 97} The lower panel shows that exposure of Hupki MEF to AA⁹² induces a similar mutational profile. Pooled data from multiple samples are shown for each data set. (b) Mutational spectra observed in lung adenocarcinomas (ADCA) of heavy smokers (upper panel) have features in common with spectra in Hupki MEF⁹² (middle panel) and human mammary epithelial cells (HMEC, lower panel) exposed to B[a]P,⁸³ a tobacco carcinogen. (c) Spectra attributable to alkylation agents; upper panel: temozolomide treatment-related glioblastoma (TMZ GBM);⁸¹ middle panel: lung carcinoma of mice treated with methylnitrosourea (MNU);⁹⁰ lower panel: Hupki MEF cells treated with methylnitrosoguanidine (MNNG).⁹² The bar graphs to the right show strand bias ratios. Strand bias reflects transcription-coupled repair of chemically damaged DNA bases (NT, non-transcribed strand; T, transcribed strand). Asterisks indicate χ² test P-values for strand bias significance (*P<10E−5; **P<10E−20; ***P<10E−320; P=0 for UTUC Taiwan, in top panel of (a)). Note the less pronounced transcriptional strand bias ratios associated with the effects of alkylating agents.