POLE and cancer: As expected, we observed that some of these signature-exposed cohorts had much elevated mutation rates compared to the pan-cancer baseline mutation rate, including cohorts defined by signatures associated with mismatch repair (MMR; mean of 63.5 ± standard deviation of 13.2 SNV/Mb/patient; 10.7 × the pan-cancer baseline), POLE (579.5 ± 183.9 SNV/Mb/patient; 97.4 ×), and UV (79.2 ± 66.6 SNV/Mb/patient; 13.3 ×) (Fig. 3d and Additional file 1: Fig. S1).