Whole genome sequencing of bulk and single RPE-1 cells with induced chromosomal instability

We experimentally recapitulated steps in the chromosome breakage-fusion-bridge cycle, enabling mechanistic studies and the determination of the immediate and long-term genomic consequences of bridge formation. To determine the immediate outcome(s) of chromosome bridge breakage without confounding genomic alterations during subsequent cell divisions, we employed a combination of live-cell imaging with single-cell whole-genome sequencing (Look-Seq). Additionally, we sequenced populations grown up from single cells with a chromosome bridge to search for subclonal heterogeneity indicative of ongoing genome instability.