Fig. 3: Structural variant (SV) breakpoints (SVBPs) are enriched at TOP2B binding sites in cancer genomes.

a Comparison of SVBP frequency in TOP2B binding sites in pooled pan-cancer data from primary cancers and metastases. TOP2B-bound sites and non-bound sites were compared (TOP2B-CTCF-RAD21 vs CTCF-RAD21, TOP2B-RAD21 vs RAD21-only). As genome-wide controls, tiled genomic windows of matching size were used. b Frequency of SVBPs in TOP2B binding sites relative to functional activity at the sites. TOP2B binding sites were grouped into four bins by pan-cancer gene expression or chromatin interaction frequency. c Frequency of SVBPs in TOP2B binding sites with functional annotations: TOP2B conservation in mice, constitutive CTCF binding in human tissues, or DSB activity. P-values from one-tailed Wilcoxon tests are shown in panels (a–c). d Analysis of SVBPs in TOP2B-CTCF-RAD21 and TOP2B-RAD21 sites relative to small mutations. Sites were compared to control sites lacking TOP2B binding using two-tailed hypergeometric tests and filtered results are shown (FDR < 0.05). Enrichment scores represent directional significance such that sites with enriched mutations are on the right and depleted sites on the left (OR, odds ratio). e Relative distances of binding site midpoints and the closest SV breakpoints. Pooled SV breakpoints from HMF and PCAWG datasets within 1 kbps from site midpoints were included. The dotted line corresponds to the 600 bps window defining binding sites in this study (i.e., ±300 bps). Boxplots span interquartile range (IQR; 25–75%), lines show median values, whiskers show values within 1.5x IQR, and site counts are shown below. P-values are from one-tailed Wilcoxon tests. Source data are provided as Source Data files.