Exome sequencing and processing

Whole exome sequencing was performed on DNA purified from tumor tissue and normal blood as described⁹, with the exception of CRUK0063_BR_T1-R1. This capture was performed according to the manufacturer’s 200 ng DNA protocol (Agilent). Annotated SNV calls are available in Supplementary Table 3 in Jamal-Hanjani et al. 2017⁹. For this study, one relapse sample was acquired through metastatic tissue biopsies from each of four patients (CRUK0035, CRUK0041, CRUK0044, CRUK0063). Additionally, six metastatic samples were acquired at post mortem examination of CRUK0063. Genomic DNA was purified from all tissue samples, and processed through the TRACERx bioinformatics pipeline as described⁹. Annotated SNV calls are available in Supplementary Table 4.