Fig. 2: Mutational processes underlying the increased mutation load in pediatric t-MN (n = 44).

a The contribution of each single base substitution signature to t-MN blasts of each patient, obtained after bootstrapped (n = 100) refitting of signatures that were extracted by non-negative matrix factorization. The first bar below the plot represents the first diagnosis (abbreviations conform Fig. 1a), the second bar notes if a pathogenic germline mutation was found, the third bar represents the treatment category (>150 mutations of that treatment type, or otherwise “clock-like”) and the last bar indicates the country in which the sample was collected. b Mutation accumulation of t-MN (colored dots) compared to the baseline of healthy blood cells (black dots). The color is similar to the grouping in (a). c The ratio of the number of observed versus expected single base substitutions in all t-MN samples within a specific signature-category (as in (b)). N = 44. Here and in all other figures, the box plots depict the median (center line), 25th and 75th percentiles (box), and the largest values, no more than 1.5 * the interquartile range (whiskers). d The 96-trinucleotide single base substitution profiles of SBSD-G and the profile of the previously defined signature sbs25 (Pich et al.³¹). e The probability that different driver mutations (n = 59) were caused by treatment-related or clock-like signatures. Colors are similar to signatures in (a). Source data are provided as a Source Data file.