When considering alterations at pathway level, genes involved in cell cycle regulation (such as TP53, CCND1, CDK6, RB1, and CDKN2A) were frequently altered in the early stage of ESCC, whereas genes in RTK/RAS/PI3K tended to undergo alterations throughout the process of ESCC evolution [44]. The gene discussed is PIK3CA; the disease is esophageal squamous cell carcinoma.