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). This evidence concerns the gene GRIN2B and esophageal squamous cell carcinoma.