Genes regulating cell cycle (CDKN2A) [9], receptors to growth factors (SMAD4) [10], chromatin remodeling (ARID1A) [11] and Racl pathway (ELMO1 and DOCK2) [12] are significantly mutated in EAC, while ESCC is characterized by alterations in the mechanisms controlling terminal differentiation (KMT2D) and proliferation (FAT1 and FAT2) [13]. The gene discussed is KMT2D; the disease is esophageal squamous cell carcinoma.