Significant differences in the mutation frequencies of NOTCH1 and NOTCH2 (more frequent in PNM than in ESCC); copy number variations at both the gene and chromosomal arm level; and mutations in cancer-related HIPPO, WNT and NRF2 signaling pathways (more frequent in ESCC than in PNM) were observed. Here, NOTCH1 is linked to esophageal squamous cell carcinoma.