The frequencies of differential methylation events were then correlated with recurrent ESCC genomic variants that we have previously identified.25 We found that hyper-methylation events were significantly correlated with somatic mutations in the genes RB1, NOTCH1, CDKN2A and PIK3CA, 3q26.32, 7p22.3 and 14q13.3 amplifications and 2q22.1 deletions; hypo-methylation events were significantly correlated with somatic mutations in the genes CREBBP and NOTCH3, 19q13.12 amplifications and 3p14.2 and 13q14.3 deletions (Fig. 3b, c and Supplementary Data S2, 3). Here, NOTCH3 is linked to esophageal squamous cell carcinoma.