Figure 3

Aristolochic acid signatures in upper urinary-tract urothelial cancer and hepatocellular carcinoma. (a,b) Mean counts of each of six different somatic single-nucleotide mutations in exome data from (a) AA-associated UTUCs (AA-UTUC, n = 9) and (b) gastric cancers (n = 15). (c,d) Trinucleotide contexts for somatic mutations in (c) AA-UTUCs (n = 9) and (d) gastric cancers (n = 15). The height of each bar (the y axis) represents the proportion of all observed mutations that fall into a particular trinucleotide mutational class, for example CAG > CTG and TAG > CTG (indicated). Along the x axis the mutations are organized first by the nucleotide mutation itself: C > T (blue bars), C > G (black bars), C > A (red bars), A > T (gray bars), A > G (green bars), A > C (pink bars). For each single-nucleotide mutation (such as A > T) there are 16 possible trinucleotide contexts (AAA > ATA, AAC > ATC, and so on) The heights of the bars indicate the observed proportions of mutations aggregated over all exomes studied. (e,f) Mean counts of somatic single-nucleotide mutations in (e) AA-associated UTUCs (n = 9) and (f) gastric cancer (n = 15), shown separately for non-transcribed (N) and transcribed (T) strands. The lower mutation counts on the transcribed strand suggest transcription-coupled repair (see main text). (f) Analogous data for gastric cancer do not show strand bias (n = 15). (g) Probable AA-exposed HCCs show a preponderance of A > T mutations with strand bias similar to that observed in AA-associated UTUCs (n = 11). (h) Trinucleotide context for mutations in probable AA-exposed HCC is highly similar to that for AA-associated UTUCs (c). Plotted using data from [16].