Concerning genomic events, alterations of histone-modifying genes (KMT2D, KMT2C, EP300, CREBBP, SRCAP, KDM6A, KMT2A, NSD1, KMT2E, BAP1, ATRX, KDM3A), found to be mutated in 38.5% of cases, are among the most frequently mutated genes in ESCC [33]. Here, CREBBP is linked to esophageal squamous cell carcinoma.