Fig. 1

Identification of APOBEC-associated hotspot mutations and their landscape in bladder cancer. a Workflow to identify APOBEC-associated hotspot mutations (n = 44) in 602 published exome-sequenced bladder cancers. Hotspot mutations were defined as counts ≥ 4 (‘Methods’). APOBEC signature was quantified by the sum of fraction scores of COSMIC signatures 2 and 13 [3]. In our method, we compared the sum of APOBEC signature fraction scores between tumours bearing a given candidate hotspot mutation corresponding to an APOBEC-type motif (TCN → T [G/T]N) and tumours without any of such candidate mutations. The method from Letouzé et al. estimates the probability of each mutation being due to each mutational process without restriction of stringent motifs [35]. b Proportion of APOBEC-associated hotspot mutation events among overall hotspot mutation events in tumours bearing at least one of 130 hotspot mutations (counts ≥ 4) in BCa. c Comparison of mutation frequencies between APOBEC-associated hotspot mutations (n = 44) and other hotspot mutations (n = 86). P value: Wilcoxon test