Extended Data Figure 10 – Models of Chromosome Evolution During Primary Tumor Expansion.

(a-c) Three models of chromosome evolution dynamics during the expansion of primary TNBC tumors, with schematic plots of chromosome accumulation over time in left panels and Muller plots of clonal frequencies in right panels. (a) Gradual model of copy number evolution, in which CNAs are acquired sequentially throughout tumor progression leading to the expansion of successive subclones over time (b) Punctuated copy number evolution model, in which an initial burst of instability generates a large number of CNAs and subclones that undergo stable expansions to form the primary tumor mass, with no (or few) new CNAs acquired after the initial burst (c) Model of punctuated evolution and transient instability, in which the early acquisition of TP53 mutations and genome doubling lead to a burst of genomic instability in which a large number of CNA events are acquired and subclones are generated. These events are followed by a period of transient instability and ongoing copy number evolution during the expansion of the primary tumor mass, which leads to the generation of additional subclones and genomic diversity.