Fig. 3

Analysis of somatic copy number alterations and localised hypermutation in tumour and plasma. Absolute copy number calls from tumour and plasma samples are shown in A. Gains in overall copy number are highlighted in red and losses of copy number are shown in blue. Genome-wide somatic copy number calls in tumour (left) and matched baseline (pre-treatment) plasma (right) from patient 45 are displayed in B. Amplifications and copy number gains at the ERBB2 locus on chromosome 17 were observed in both tumour and plasma from this patient. C, D Rainfall plots showing the distribution of single somatic substitutions in tumour (C) and combined plasma (D) from patient 45, with arrows highlighting the presence of a unique kataegis region on chromosome 17 co-localising with ERBB2 amplification. This region was enriched for T > G substitutions and contained ERBB2 driver mutations in tumour, which were also detected in ctDNA. Inter-mutation distance is presented on the vertical axis and the number of mutations in each sample on the horizontal axis