Extended Data Fig. 8. Selective and ordered patterns of genome evolution during cancer initiation.
a, Unique breakpoint patterns associated with chromosome 11 deletions identify independent p53 LOH lineages. Grey dots illustrate normalized raw read count values. Black lines illustrate segmented data. Vertical grey line denotes location of Trp53. Number of single cells sequenced representing each unique breakpoint event is provided. b, Boxplot quantification of unique lineages based on chromosome 11 deletion breakpoints in Pre-SP diploid cells (n = 7 samples) compared to PDAC-SP polyploid cells (n = 4 samples). Mann-Whitney U two-sided test of significance for number of LOH events in Pre-tumour and PDAC-SP samples, p-value = 0.03. c, Boxplot quantification of normalized read count mappability data from a census single cell genotyping approach (Methods) from PDAC-DP (n = 6), PDAC-SP (n = 6), and Pre-tumour SP (n = 7) single-cell sequencing at eGFP, Trp53, mKate, and Clp2 (control) sequences. d, Zoom in chromosomal views illustrating intra- (from within one animal) and inter- (between different animals) alteration heterogeneity of Kras gains (chromosome 6). e, Boxplot quantification of acquired copy number alterations detected in single-cell sequencing data from DP (n = 6), Pre-SP diploids (n = 7), and PDAC-SP samples (n = 6). p-value < 0.05 for all pairwise two-sided Mann-Whitney U test of significance with exact values provided in figure. f, Genome-wide illustration of independent genome doubling events observed in polyploid cells from non-tumour bearing sample P1 (left panels) and P2 (right panels). Red Arrows denote distinguishing p53 LOH events. g, Frequency plot depiction of diploid SP PDACs from the KPCLOH model (n = 7). Box plots are as defined in Fig. 1.