We next investigated the dynamic patterns of somatic mutations in ESCC-related genes during combined therapies and identified 75 driver mutations based on previously reported criteria (Supplemental Table 6 and refs. 53, 54), including several well-known ESCC-implicated genes, such as TP53, NOTCH1, FAT1, CDKN2A, and PIK3CA (Figure 2). This evidence concerns the gene NOTCH1 and esophageal squamous cell carcinoma.