Supplementary Figure 3: Clonal structure and evolutionary dynamics of uncharacterized HER2 (ERBB2) mutations.

Clonal dynamics are shown for three metastatic samples with uncharacterized HER2 (ERBB2) mutations by comparing the metastatic clonal cell fraction/CCF (y axis) to the matched primary CCF (x axis). ERBB2 mutations are mapped to metastatic acquired clones in all three patients (colored in red, upper left corner) while not detected in the matched primary (CCF ~ 0). 'Truncal’ mutations that are shared between metastatic and primary tumors are found in all patients, demonstrating that the primary and metastatic samples are clonally related (colored in gray, upper right corner; CCF ~ 1 in both primary and metastatic samples). Primary-specific mutations are found in clones that were dominant in the primary tumor but not observed in the metastatic tumor (colored in blue). The phylogenetic relationships among clones are reconstructed for each patient starting from the normal cell (white circle) connected to the ancestral cancer cells (gray trunk). The phylogenetic divergence of the primary clones and subclones is depicted with blue edges, and that of the metastatic clones and subclones in red. Selected mutations in cancer genes are marked on the corresponding branches of the cancer phylogeny.