Fig. 2: TMB and mutational processes.

a, Cumulative distribution function plot (samples were ranked independently for each variant type) of TMB for each cancer type for SBS (blue), IDs (green) and DBS (red). The horizontal lines represent median values. The fold-change labels are included only when two-sided Mann–Whitney comparison renders a significant adjusted P < 0.05. b, SBS mutational spectra of patients with metastatic (top) and primary (bottom) tumours. Patients are ordered according to their TMB. DDRD, DNA damage repair deficiency; ROS, reactive oxygen species. c, Moon plot representing the SBS mutational burden differences attributed to each mutational signature in metastatic (main plot, left) and primary (main plot, right) tumours. The edge thickness and colours represent significant differences (two-sided Mann–Whitney adjusted P < 0.05, ±1.4× fold change) and the direction of the enrichment, respectively. The size of the circles are proportionate to the mutation burden difference. The bars on the right indicate the number of metastatic cancer types with a mutational signature with significant enrichment. The top stacked bars represent the cumulative signature exposure difference. The thicker bar edge lines represent significance. Bars are coloured according to the annotated aetiology. Only mutational signatures with known aetiology or with at least one cancer type with significant metastatic enrichment are included. 5-FU, 5-fluorouracil; 5mC, 5-methylcytosine; MMRd, mismatch repair deficiency.