Through this extensive analysis, they identified a mutational signature unique in ESCC, linker to alcohol intake and genetic variants in alcohol-metabolizing enzymes; the alcohol-driven ESCCs were characterized by a high frequency of mutations at the level of TP53, EP300, PTCH1, NOTCH3, TGFBR2 and ZNF750 [57]. This evidence concerns the gene NOTCH3 and esophageal squamous cell carcinoma.