Fig. 6: Selected breast cancer-related SNPs with potential regulatory function.

a, d, g show evidence for our proposed hypothesis explaining the underlying mechanism of action for the studied variants. Each panel contains multiple tracks characterizing the region harboring the variant. From top to bottom, horizontal tracks depict the chromosomal location of the 1 kb region, color coded motif-based estimate of binding strength for all TFs included in the models (Binding strength), locations of common SNPs, breast tissue/cancer eQTLs and somatic variants (Variants) present in the vicinity of the studied variant highlighted in gray, predicted change in binding strength due to a variant, measured by the change in LLR score of a binding site normalized by maximum LLR score among all sites of that TF (Binding change), predicted percentile change in enhancer activity due to a variant (Activity change), presence or absence of transcribed eRNA after E2 stimulation of MCF7 cells (eRNA after E2), and presence or absence of ERα, H3K27Ac and other TF ChIP peaks. a Schematic representation of the enhancer region containing rs3809260 variant (highlighted). b Tested variant enhancer differs from wild-type enhancer in a putative FOXA1 binding site sequence; three nucleotide changes (including the SNP) create a consensus FOXA1 site. c Results of dual-luciferase assays on WT enhancer (shown in a) and variant (tested) enhancer, in MCF7 cells without or with E2 treatment. Note that experiments were done in duplicates. d Schematic representation of the enhancer region containing rs12890411 variant (highlighted). e Tested variant enhancer differs from wild-type in a putative RELA binding site sequence; a strong RELA site is abolished in the variant. f Results of dual-luciferase assays on WT enhancer (shown in d) and variant (tested) enhancer, with and without E2 treatment. g Schematic representation of the enhancer region harboring the somatic variant chr19_10502235_G_C (highlighted). h Change in putative NR5A2 binding site sequence in the tested variant enhancer; a strong NR5A2 site is abolished. i Results of dual-luciferase assays on WT enhancer (shown in g) and variant (tested) enhancer, in MCF7 cells with and without E2 treatment.