Figure 1.

When patients with the same cancer type have different exposure histories, the mutation patterns in their tumours can be strikingly different. Two representative cases of upper urinary tract urothelial tumours from regions of either low or high risk of exposure to the carcinogen aristolochic acid⁹⁷ were analysed using whole-exome sequencing. The single-base substitution distribution spectra are shown on top. Performing NMF on the studied case series identified three distinct mutational signatures (A, B and C; middle panel). The pie charts show the proportionate contribution of individual signatures to the mutational load in each tumour. The absence of signature A in case 1 argues that the two tumours have distinct aetiologies.