Fig. 3: Chemotherapy-induced mutations in healthy colorectal ASCs.

a The distinct extracted de novo SBS signature in treated healthy colorectal tissue resembles a mix of the COSMIC 5-FU and platinum mutation signatures (cosine sim = 0.88). b Box and whisker plot indicating the relative mutation contribution of the treated specific SBS mutation signature from colorectal ASCs between CapOx-treated (n = 7) and untreated (n = 5) colorectal donors. The here shown box and whiskers plot displays the first and the third quartiles (top and bottom of the box), the median (vertical line inside the box), the extremes (whiskers) and the single data points (single dots). A Wilcoxon rank-sum test between every cohort was performed and the p value is illustrated at the top of the plot. c 5-FU and platinum SBS and DBS mutation contributions (y axis) for each donor as a function of age (x axis). Each data point represents the mean mutation contribution per donor, the error bars represent the standard deviation and the color depicts the treatment history. The number of sequenced ASC per donor (n) varies from 1 up to 6 samples and is listed in Fig. 1a. The 5-FU and platinum mutation contributions are derived with refitting on the well-established platinum COSMIC signatures. d The distinct extracted de novo DBS signature in CapOx-treated ASCs from (n = 7) healthy colorectal donors. This signature resembles the COSMIC platinum DBS-5 mutation signature (cosine sim = 0.81). e Box and whisker plot indicating the relative mutation contribution of the treated specific DBS mutation signature from colorectal ASCs between oxaliplatin-treated (n = 7) and untreated (n = 5) donors. A Wilcoxon rank-sum test between every cohort was performed and the p value is illustrated at the top of the plot. f Scatterplot showing the relation between platinum SBS (x axis) and DBS (y axis) mutations, derived with refitting on the well-established platinum COSMIC signatures. The brown line displays the least-squares linear fit of (n = 25) oxaliplatin-treated ASCs while the shaded region represents the 95% confidence interval of the fit (Pearson’s r = 0.88). g Scatterplot showing the relation between the number of CapOx treatments (x axis) and platinum SBS mutations (y axis) of the (n = 25) oxaliplatin-treated ASCs. The p value of the treatment count effect in the LMM that controls for donor ID (two-tailed t-test) is 0.03. The shaded area represents the standard deviation of the LMM by treatment count effect. Source data are provided as a Source Data file.