At the level of single genes, the most remarkable differences were observed for a set of genes (ERBB2, KRAS, SMAD4 and EGFR) less mutated in ESCC than in EAC, while another set of genes (PTEN, PIK3CA, CCND1, NFE2L2, NOTCH1, MLL2 and SOX2) is more mutated in ESCC than in EAC [63]. The gene discussed is SMAD4; the disease is esophageal squamous cell carcinoma.