Extended Data Fig. 1: Hartwig sample workflow, biopsy locations and sequence coverage.

a, Sample workflow from patient to high-quality WGS data. A total of 4,018 patients were enrolled in the study between April 2016 and April 2018. For 9% of patients, no blood and/or biopsy material was obtained, mostly because conditions of patients prohibited further study participation. Up to four fresh-frozen biopsies were obtained per patient, and were sequentially analysed to identify a biopsy with more than 30% tumour cellularity as determined by routine histology assessment. For 859 patients, no suitable biopsy was obtained, and 2,796 patients were further processed for WGS analysis. In total, 44 and 29 samples failed in either DNA isolation or library preparation and raw WGS data quality control tests, respectively. For a further 385 samples, the WGS data were of good quality, but the determination of tumour purity based on WGS data (PURity & PLoidy Estimator; PURPLE) was less than 20%, making reliable and comprehensive somatic variant calling impossible and were therefore excluded. Eventually, 2,338 pairs of tumour and normal tissue samples with high-quality WGS data were obtained, which were supplemented with 182 pairs from pre-April 2016, adding up to 2,520 pairs of tumour and normal samples that were included in this study. b, Breakdown of cohort by biopsy ___location. Tumour biopsies were taken from a broad range of locations. Primary tumour type is shown on the left, and the biopsy ___location on the right. c, Distribution of sample sequencing depth for tumour and blood reference samples (n = 2,520 independent samples for each category). The median for each is indicated by a horizontal bar.