CDK4 and cancer: In this model, expression of HRASG12V and Cdk4, which reflect Ras-MAP kinase activation [23–25, 35] as well as inactivation of the CDKN2A-mediated G1 restraints characteristic of cSCC [18–20, 24, 36, 37] (Fig. 1a and SI Appendix, Table S2), are sufficient to drive cancer progression by normal diploid epidermal keratinocytes.