KEAP1 and esophageal squamous cell carcinoma: Other previously identified hotspots in ESCC, including the silent mutations of R80X, R58X, and W110X in CDKN2A, E545K, and H1047R in PIK3CA30, and the mutations in KEAP1 binding motifs of NFE2L231, were also confirmed in ESCC-META dataset (Fig. 5a).