Genomic and transcriptomic profiling of clonal populations derived from homotypic cell-cell fusion in triple-negative breast cancer

To investigate the genomic and transcriptomic impact of homotypic cell-cell fusion, we compared copy number variation (CNV) of eight single-cell isolated clonal cell populations (controls) to eight fusion-derived clonal populations (fusions) via low-pass whole-genome sequencing (WGS) in two triple-negative breast cancer (TNBC) cell lines (HCC1806 and MDA-MB-231). Additionally, we co-cultured pairs of control clonal populations and single-cell isolated spontaneously arising fusion events to generate clonal fusion populations with matched parental controls, referred to as matched fusion-parent trios.

All fusion clonal populations from matched trios were also profiled using WGS to analyze CNV versus matched parents, and all surviving fusion and control clonal populations from the matched trios were profiled in biological triplicate by TagSeq (3' tag-based RNA-seq) for transcriptomic analysis.