In correlating the progression Z-scores of the breast cancers to clinical tumour features, including ER, PR and HER2 status, as well as KI67, tumour size, age and clinical outcome, we observed a significant positive association with proliferation (KI67; Fig. 6b, Supplementary Fig. 16B and Supplementary Table 5), which was strongest for the hypervariable and hypermethylated DVMCs. This evidence concerns the gene ESR1 and neoplasm.