We examined the mutational frequencies of the most frequently mutated genes in ESCC, including TP53 (78%), TTN (35%), MUC16 (16%), NOTCH1 (16%), CSMD3 (15%), KMT2D (11%), FAT1 (10%), and LRP1B (10%). This evidence concerns the gene KMT2D and esophageal squamous cell carcinoma.