These studies depicted the general mutational landscape of ESCC, including the significantly mutated genes such as TP53, CDKN2A, EP300, PIK3CA, and NOTCH1, the commonly influenced pathways such as PI3K-AKT axis, cell cycle, and histone modification, and the commonly identified age-related and APOBEC enzymes-related mutational signatures2–20. Here, TP53 is linked to esophageal squamous cell carcinoma.