We summarized the mutated genes by their related oncogenic pathways (Fig. 3a) and found that 38.1% ESCC patients had at least one mutation in Hippo pathway (including FAT1, FAT2, and FAT3), 38.6% in histone modification, 33.8% in NOCTH pathway (KMT2D, KMT2C, EP300, and CREBBP), 19.8% in RTK-RAS pathway (ERBB4 and ROS1), 17.6% in cell cycle pathway (CDKN2A, RB1), 15.3% in PI3K pathway (PIK3CA), and 12.6% in Nrf2 pathway (NFE2L2, KEAP1). Here, EP300 is linked to esophageal squamous cell carcinoma.