Fig. 4: Selection in metastasis.

a, Cluster dispersion and maximum cancer cell fraction (CCF) across primary tumour regions in the subclonal seeding clusters versus non-seeding clusters in metastasizing tumours. b, Examples of seeding cluster dispersion across primary tumour regions illustrated by one clone-map per region. CRUK0702 demonstrates a single dominant seeding cluster (purple), dispersed across two primary tumour regions. CRUK0063 highlights two dominant (purple and yellow) and one minor seeding cluster (pink). c, Cohort-level selection (n = 111 genes) of seeding (purple) versus primary-unique mutations from metastasizing tumours (green) versus subclonal non-metastasizing primary tumour mutations (grey). The dots represent dN/dS estimates; the asterisks indicate values that are significantly different from 1. d, Gene-level dN/dS values of seeding mutations versus combined primary-unique/non-metastasizing primary tumour mutations for all histologies. A dN/dS odds ratio (OR) of >2 indicates a seeding favoured gene; <0.5 is primary favoured; 0.5–2 is classified as both primary and seeding favoured. Purple and green gene names represent significant enrichment in seeding and non-seeding mutations, respectively. The lines indicate the 95% CIs. e, Paired primary tumour–metastasis (met) mutation analysis. Metastasis favoured mutations are defined as having a higher clonality in metastases compared with the primary tumour; primary favoured if the clonality is higher in the primary tumour; the remaining were classified as maintained; background refers to mutations in non-cancer genes. f, The GISTIC2.0 score difference between the unpaired metastases and non-metastasizing cohorts plotted against the false-discovery rate of the G-score in the metastases cohort for cancer genes. Amplified genes are shown in red; deleted genes are shown in blue. Horizontal dotted lines indicate p = 0.05 g, Paired SCNA analysis of cancer genes that were found to be significant in f. An amplification/deletion was classified as metastasis favoured if it was present in the metastasis and absent in the primary tumour, primary favoured if present in the primary tumour but not the metastasis, or otherwise defined as maintained. Only tumours that had at least one copy number event in the gene in any sample were counted. For e and g, significant genes (multinomial test; p < 0.05) are shown in bold; asterisks represent significance after multiple-testing correction (q < 0.05); numbers in parentheses indicate number of events.