Figure 4: ESR1-enhancer DNA hypermethylation in acquired endocrine resistance in human breast cancer.

(a–e) (Left panel) A scatter plot showing the methylation of individual CpG sites across the ESR1-enhancer region of interest ((a)-DAXX—Chr6: 33288296-33288372; (b)-MSI2—Chr17: 55371693-55371786; (c)-NCOR2—Chr12: 124844786-124844883; (d)-RXRA—Chr9: 137252867-137252967; (e)-C8orf46—Chr8: 67425069-67425134) in three primary luminal A breast cancers from patients that received adjuvant endocrine therapy and exhibited RFS (green), three primary luminal A breast cancers from patients that relapsed following adjuvant endocrine therapy, defined as no n/RFS (blue) and their matched local relapse (red). Each dot represents the % methylation at an individual CpG site for a single patient and the lines represent the average methylation for the region in primary RFS (green), primary n/RFS (blue) and matched recurrent tumours (red). (Right panel) Box plots showing the distribution of methylation values across the ESR1-enhancer region depicted in the left panel for RFS (green), prognosis/RFS (blue) and matched recurrent tumours (red); P values correspond to t-test comparison between RFS versus n/RFS, and n/RFS versus relapse tumours. (The whiskers of the box plots extend to the most extreme data point, which is no more than 1.5 × interquartile range from the box).