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Hi-C detects novel structural variants in HL-60 and HL-60/S4 cell lines

Cancer cell lines often have large structural variants (SVs) that evolve over time. There are many reported differences in large scale SVs between HL-60 and HL-60/S4, cell lines derived from the same acute promyelocytic leukemia sample. However, the stability and variability of inter- and intra-chromosomal SVs between different sources is unknown. Here, we used Hi-C and RNA-seq to identify and compare large SVs in HL-60 and HL-60/S4 cell lines. Comparisons with previously reported karyotypes identified two non-canonical SVs in HL-60. Ten previously unreported SVs were identified in HL-60/S4. The unreported SVs were generally small enough to be plausibly undetected with traditional karyotyping methods. An expansion centered on MYC was found in a novel genomic location in HL-60. The HL-60 cell line has more within-line structural variation than the HL-60/S4 derivative cell line. HL-60 and HL-60/S4 karyotypes are generally consistent with the current literature, with some exceptions. Hic_breakfinder is an effective tool for identifying all SVs, but intra-chromosomal SVs are less reliably detected across different samples. The orientation of SV patterns, and strandedness of gene fusions, allowed us to differentiate inversions from other forms of intra-chromosomal SV. Visual inspection of Hi-C heatmap patterns allow further characterization of SVs without additional methods, although orthogonal information such as gene fusions contribute to the characterization.