Fig. 6: Segmental copy-number patterns in BE/EAC genomes consistent with the outcomes of multigenerational breakage-fusion-bridge cycles.

Arabic numbers represent outcomes of different sequences of BFB evolution as labeled in Supplementary Fig. 5D. Schematic diagrams of altered chromosomes are drawn according to the segmental DNA copy number. A (Top) Terminal deletion -> terminal duplication; (bottom) paracentric deletion -> two duplications near the centromeric break end. B (Top) Pericentric retention -> duplication at the q-terminus; (middle) paracentric deletion -> whole-chromosome duplication of the centromeric segment; (bottom) whole-chromosome duplication -> pericentric loss + terminal gain -> whole-genome duplication. Magenta lines represent joining between broken fragments. See Supplementary Fig. 6 for more examples. C Complementary copy-number gain and loss at a single breakpoint (dashed line) in HGD and IMEAC reflect two broken pieces of a single dicentric chromosome. The focally amplified region on the telomeric end in IMEAC is consistent with BFB amplifications either preceding or after the breakage event. D A series of terminal deletions on the same parental chromosome present in five lesions from patient 2. The proximal boundaries of the subclonal DNA loss near the 4q-terminus in HGD2 and clonal DNA loss in IMEAC2 suggest that IMEAC2 may have evolved from a subclone in HGD2. See Supplementary Fig. 7 for examples of the same pattern revealed in experimental BFB evolution. E Summary of SCNAs in related BE/EAC genomes reflecting divergent/branching BFB outcomes. See Supplementary Data 6 and “Online Data” for the copy-number plots of each instance.