Previous reports have confirmed that mutations in P53, CDKN2A, RAS, NOTCH1, and NOTCH2 are closely related to cSCC [6–9, 26]; however, the underlying molecular mechanisms behind the aggressive progression of cSCC subpopulations remain to be unveiled, which might account for the high mortality rate of cSCC in NMSC [27]. Here, CDKN2A is linked to skin squamous cell carcinoma.