Cohort overview and complex genomic rearrangements detected by our SV detection workflow. (A) Samples from patients with CK-AML (n = 11) were subjected to genomic sequencing (Hi-C and ONT-GS) for SV detection. In addition, healthy CD34⁺ stem cell donors (n = 5) and the CK-AML samples were RNA-sequenced (Illumina RNA-Seq and ONT cDNA Seq) to study the functional consequences of the SVs. (B-C) Hi-C maps of patient CK1-Mut, chromosome 7/8 trans-map (B) and chromosome 7 cis-map (C). Hi-C breakend regions were inferred based on signal intensity at the breakends and are marked by black squares (named “a” to “h” for simplicity). Region d was shown to only harbor breakpoint-like patterns in the integrated analysis with NanoVar data. (D) Zoomed in detail of Hi-C maps showing breakends detected by both Hi-C and NanoVar (green squares with black squares inside). In these cases, the NanoVar SV calls were found to map in the same 10 kb range in which the BND were located estimated based on Hi-C. In region “e,” we observed an indirect BND-like structure in the upper right corner (black square) without a corresponding NanoVar SV call. Interestingly, a NanoVar SV pointed out to a small fragment (<5 kb, named N2), also visible in Hi-C but missed in the primary visual inspection. This fragment represents the actual trans-map BND of chromosome 7/8 in breakpoint region “e” and is depicted also by a black square inside a green square (for Hi-C and NanoVar support) here. The previously assumed breakend in region “e” was shown to be connected to the N2 fragment in cis (data not shown). (E) Based on the Hi-C pattern, we identified 2 regimes of complexity in our cohort: all of the CK-AML cases that were TP53 mutated displayed chromothriptic rearrangements, whereas most cases that were TP53 wildtype showed far less complexity. Hi-C BND regions are highlighted by black squares.