In order to identify interactome hotspots of simultaneous differential methylation and gene expression associated with ER+ breast cancer, we applied our FEM algorithm [11] (Fig. 1a) to the ER+ breast cancer subset of The Cancer Genome Atlas (TCGA), encompassing Illumina Infinium 450K DNA methylation and RNA-Seq data for 111 normal adjacent and 724 cancer samples. This evidence concerns the gene ESR1 and breast carcinoma.