Fig. 3

Short variants reveal high-resolution phylogenetic relationships among all tumor biopsies, and early subclonal expansion and migration events. A Reconstructed phylogenetic tree based on short variants confirms the grouping of the samples and reveals more detailed relationships among samples in groups as well as the placement of Ln7 and Ln9. BrP, BrM, and Ln1 shared variants with different samples, indicating that they are mixtures of cell populations. Three shades spanning multiple branches represent samples BrP, BrM, and Ln1. B Reconstructed subclone structures in BrP, BrM, and Ln1 show the heterogeneity of these three samples. The descendant relationship among the subclones suggests the earliest invasion was to the lung and reveal other subclone migrations and expansions from BrP. Each blue circle represents an inferred subclone. Each box represents a sample or a group of samples. C Overall migration patterns across all tumor sites, with arrow colors corresponding to metastatic waves. After the first invasion from primary breast tumor to lung (blue arrow), four metastatic waves spread the tumors to other organs