a, Definitions of the dissemination patterns of metastases at the case level, described relative to the primary tumour phylogeny. Grey arrows indicate the branches leading up to the seeding cluster(s). b, The most prevalent mode of metastatic dissemination observed is monoclonal monophyletic. Polyclonal ‘mixed’ represents cases in which a consensus dissemination pattern could not be inferred due to different possible phylogenetic tree topologies. c, At the sample level, polyclonal dissemination is more prevalent in primary LN/satellite lesions compared to recurrence/progression lesions (Fisher’s exact test, P = 0.03). d, Polyclonal dissemination is associated with a higher number of metastatic samples compared with monoclonal dissemination (median number of metastasis samples: 2 versus 1, respectively; Wilcoxon rank-sum test, P = 0.00078), sample number depicted as discrete values (left panel) or proportion (right panel). e, In cases where recurrence occurs, polyclonal dissemination is associated with extrathoracic metastasis, as identified on imaging, compared with monoclonal dissemination (n = 57 (monoclonal), n = 27 (polyclonal); Fisher’s exact test, P = 0.0056) f, Examples of cases with monoclonal (CRUK0559) and polyclonal polyphyletic (CRUK0484) dissemination patterns, both of which also demonstrate metastases being seeded from other sites of metastatic disease. The black arrows on the body map represent the routes of metastatic seeding (MACHINA). Each seeding cluster in the phylogenetic tree, as defined by our method, is assigned a unique colour that is also represented in the region clone maps. The timeline indicates the day on which the metastases were detected on imaging; the biopsy dates differ from this. For CRUK0559, the recurrence biopsy took place on day 188. For CRUK0484, the rib recurrence, scapula progression and brain progression were sampled at days 147, 433 and 582, respectively. The box plots represent the upper and lower quartiles (box limits), the median (centre line) and the vertical bars span the 5th to 95th percentiles. All tests were two-sided unless otherwise specified. LN, lymph node; RUL, right upper lobe; RLL, right lower lobe.