Fig. 4. Gene alterations within complex SV events selected in CO patients.

a CO ID 686 with complex SV in both T2 samples, which cluster together in the SNV-based parsimony tree. The phylogeny is annotated with ESAD genes of interest with functional 2+ caller mutations (multiple mutations in the same gene are appended with _a, _b), and Δ indicates chromosome copy loss of mutated allele. The complex structural rearrangement pattern of rigma²³ was detected in all four samples, whereas tyfonas (“typhoons” of high junction copy number junctions and fold back inversions²³) was only detected in the T2 sample, shown in the right panel. Within this region, CDK12 was disrupted by structural alterations and ERBB2 was within one of the highly amplified regions within this complex SV. b CO ID 163 with expanded TP53 −/− and genome doubling in all four samples. The three samples on the lower clade in the SNV-based phylogeny share a common amplified region which includes increased copies of GATA6 and surrounding genes. Total Mb SCA are indicated for each sample. CN = copy number. Source data are indicated in Figure Source Data File.