Fig. 7: Complex segmental copy-number patterns in BE/EAC genomes indicating successive chromothripsis and BFB cycles.

Arabic numbers correspond to the outcomes of different sequences of BFB evolution involving chromothripsis as labeled in Supplementary Fig. 5D. A Chromothripsis (in LGD2) and terminal duplication (EAC) occurring downstream of an ancestral paracentric deletion in patient 6. The dotted line represents the ancestral breakpoint shared by all three genomes; dashed lines represent private SCNA breakpoints. B Reciprocal distribution of segments of 14q in HGD and IMEAC lesions from patient 11. The bottom shows an enlarged view of the outlined region (dashed box). Except for a small segment near 30 Mb, all the other segments retained in the IMEAC genome are lost from the HGD genome. Dashed lines denote SCNA breakpoints with opposite retention and loss in the two genomes. The retention of the segment near 30 Mb in both genomes may arise from the distribution of DNA fragments from a partially replicated broken chromosome from a micronucleus [Zhang et al.³⁴ and Umbreit et al.³⁸]. C Four subchromosomal regions with distinct high-level DNA amplifications in IMEAC2 (same in IMEAC3) and EAC1 from patient 1. For 8p, we infer the SCNAs evolved from a single unstable ancestor chromosome based on shared SCNA breakpoints (dotted lines). For 1p and 16p, the SCNAs are related by deletions with adjacent boundaries (dashed lines). The amplified regions on 16p in EAC1 are joined to the amplified region on 18q spanning GATA6. The order of chromothripsis and amplification is determined based on whether the amplified regions are interrupted by deletions (indicating chromothripsis before amplification) or peppered with DNA losses (indicating chromothripsis after amplification). D Summary of chromothripsis and DNA amplification instances grouped by copy-number features and the inferred evolutionary sequences. The inference of chromothripsis arising either directly from or downstream of dicentric chromosome breakage is based on the span of oscillating copy-number pattern relative to entire chromosomes; instances with less certainty are annotated accordingly (“possibly downstream” or “likely direct”). See Supplementary Figs. 8 and 9 for more examples and Supplementary Data 7 for more information.