We evaluated the recurrences, impacts of protein function, and hotspots of mutations in all mutated genes (Figure 1C) and identified 6 frequently mutated genes, TP53 (95%), FCGBP (19%), FRY (18%), ZNF750 (16%), NFE2L2 (15%), and GRIN2B (10%) (Figure 2 and Supplemental Figure 3A), among which TP53, NFE2L2, and ZNF750 have been proved to drive ESCC tumorigenesis (2, 3, 17). Here, NFE2L2 is linked to esophageal squamous cell carcinoma.