CDK4 and melanoma: Our findings suggest that oral melanomas behave similarly and may evolve through two different paths driven by SV somatic changes that would lead to marked differences in therapeutic options: the first group containing “hot immune” tumors with a lower numbers of SVs would likely benefit from immunotherapy, while the second group, which contains “cold immune” tumors with a higher number of SVs would respond better to therapies targeting amplified oncogenes, such as treatment using CDK4/6 inhibitors.