Fig. 3: Distinct and ordered phases of genome evolution accompany the benign-to-malignant switch.

a, Breakpoint-based phylogenetic tree of single SP (n = 130) and DP (n = 55) cells sequenced from PDAC sample T2 (left). The red arrow indicates a split in the neighbour-joining tree and clonal sweep of SP cells. Distance is based on statistical considerations of breakpoint similarity/dissimilarity (Methods). Sweeping SP cells share a clonal relationship with a false-discovery rate (FDR) not exceeding a threshold value of t = 0.01. Right, breakpoint-based phylogenetic tree of single SP cells (n = 171) sequenced from pre-tumour sample P3. The clone track denotes a lineage that underwent genome doubling (navy). The clonal relationship between diploid and polyploid cells is computed with an FDR not exceeding a threshold value of t = 0.01. Colour codes for ploidy, lineage and copy number are provided. b, Matched H&E and immunofluorescence of lesions that underwent LMD (yellow outlines) (top). Bottom, matched copy-number profiles of lesions collected by LMD. Scale bar, 50 μm.