Fig. 1

ER binding is associated with increased somatic mutation rates in breast cancer. Heatmaps show DNase I sequencing read intensity as a measure of DNase hypersensitivity in MCF-7 cells (ENCODE) and ER ChIP-seq read intensity in 21 ER⁺ breast cancer samples profiled by Ross-Innes et al. [23]. Observed somatic mutation rates (red line) for 560 ER⁺ breast cancer patients (ICGC BRCA-EU) [4] were calculated for sites with different ER binding and DNase hypersensitivity intensity. Expected mutation rates (black line) were calculated based on tri-nucleotide compositions of corresponding genomic sequences using previously established method [15]. Fold changes (blue bar) are comparing the observed mutation rates within 200 bp of ER binding or DHS peaks with the rates in flanking regions (> 200 bp and ≤ 1 kb); corresponding P values (orange bar) were obtained using chi-square test followed by Benjamini-Hochberg adjustment. a The observed and expected mutation rates were calculated for three sets of DHS sites with comparable intensity: the sites that overlapped with ER ChIP-seq peaks (DHS w/ ERBS), the sites that overlapped with other ENCODE identified TF but not ER binding sites (DHS w/o ERBS) and finally DHS with no TF binding sites (DHS w/o TF BS). b The observed and expected somatic mutation rates for four quartiles of ER binding sites with increasing ER binding intensity are shown. c The observed and expected somatic mutation rates at ERBS shared by more than 3 patients, 2 patients, and patient-specific are shown. Fold changes and P values are shown for each set of ERBS as described above