At the somatic level, the activity of the signature 5 in the Catalogue Of Somatic Mutations In Cancer (COSMIC) is associated with the somatic ERCC2 status in urothelial tumors [19]; and the activity of the APOBEC-related mutational signature in ESCC is associated with the somatic PIK3CA and ZNF750 statuses [20, 21]; Plus, specific mutational signatures are used to predict BRCA1 and BRCA2 deficiency in breast cancer [22]. This evidence concerns the gene PIK3CA and esophageal squamous cell carcinoma.