53). The AUC values of the cfMETH predictive score in the discovery and validation cohorts were 0.89 and 0.81, respectively. When analysing 10 optimal hypo-DMRs distinguishing malignant and benign plasma samples, four genes associated with these DMRs were reported as DNA methylation biomarkers for BC (RYR2, RYR3, GABRB3 and DCDC2C). When comparing WGBS data of the BC genome with those of healthy controls, a hypomethylation pattern at the genome-wide level was found (Ref. 53). Here, RYR3 is linked to breast cancer.