The analysis of the mutational profile confirmed frequent mutations of TP53, NFE2L2, MLL2, ZNF750, NOTCH1 and TGFBR2 in ESCC, while in EAC frequent are the mutations of TP53, CDKN2A, ARID1A, SMAD4 and ERBB2 [64]. Here, SMAD4 is linked to esophageal squamous cell carcinoma.