Extended Data Fig. 5: Evolution of clonal HMEC lineages in long-term culture.
From: Chromosome evolution screens recapitulate tissue-specific tumor aneuploidy patterns
(a) Copy number plots for 2 pure diploid HMEC clones, one diploid clone mix, and 12 2N-range aneuploid HMEC clones grown in culture over time. The top bar of each panel represents the original clonal copy number profile (PD0). Most clones were grown in multiple replicate cultures, for up to 40 population doublings. Several lineages were propagated longer than 40 PDs. (b) Copy number plots for 13 4N-range aneuploid HMEC clones grown in culture over time. The top bar of each panel represents the original clonal copy number profile (PD0). Clones were grown in duplicate or triplicate for most lineages, for up to 40 population doublings. (c) Copy number plots for CQ daughter clone in vitro evolution experiments. Same color bar as for (b). (d) Net chromosome arm gain/loss frequencies after in vitro evolution experiments (newly selected events only) compared to net gain/loss frequencies in the breast cancer TCGA cohort. Whole chromosome aneuploidies are also counted towards net gain/loss frequencies plotted by arm. For the HMEC frequency calculations, each copy comprising multi-copy events are counted towards the total events, and net event sums are divided by the total number of evolved lineage experiments (n = 90). For breast cancer frequency calculations, at least 50% of the arm must be gained/lost to count as an arm-level event. BRCA; n = 722 samples. Pearson’s correlation coefficient (r = 0.574) and associated P value (P = 8.84 × 10−5) for the correlation are shown. Dashed line indicates linear regression model of the data. 16p is highlighted for its opposite behavior in HMECs (deleted as part of whole chromosome 16 loss) and breast cancers (gained), however +16p is associated with immune evasion tumors (see Fig. 2e).
