ESR1 and neoplasm: Similarly, the ESR1 (Fig. 4d and Supplementary Fig. 4e) and MSI2 (Supplementary Fig. 4f−h) gene loci exemplify a hypermethylated DMR, which is associated with loss of local interactions and located at an ER-bound enhancer region in TAMRs and ER+ endocrine-resistant clinical tumour samples as compared to their matched primary tumours.