Exome sequencing revealed prevalent mutations in the coding regions of TP53 of patients with ESCC and, along with low-frequency mutations in some other genes (e.g., NOTCH1, NFE2L2, KMT2D, CDKN2A) [8], suggesting the involvement of additional risk factors like transcriptome remodeling in the development of ESCC. This evidence concerns the gene KMT2D and esophageal squamous cell carcinoma.