Of these histone modifier genes, seven genes including MLL2 (12.9%), EP300 (10.8%), RB1 (8.9%), KDM6A (6.2%), MLL3 (5.5%), PRDM9 (5.5%), CREBBP (5.2%) have higher mutation frequency more than 5% in ESCC (Figure 1A). This evidence concerns the gene RB1 and esophageal squamous cell carcinoma.