Tyr-Cre approaches targeting NRAS or BRAF genes also successfully generate cutaneous melanomas after concurrent deletion of tumor suppressor genes Ink4a/Arf or Pten. The TCGA reveals the distinct heterogeneity and high mutational burden of melanoma, which raises a limitation as GEMM models may not reflect the mutational burden found in human patient tumors. The gene discussed is CDKN2A; the disease is cutaneous melanoma.