Our lab is pinpointing these early events, which occur decades before tumors appear. So far, there seem to be two pathways, with different requirements for genes like ARF and BAX .
Apoptosis is signaled by UV photoproducts in actively transcribed genes.
Our model is that apoptosis of stem cells after UV allows an adjacent TP53 -mutant cell to encroach into the vacated stem cell compartments. Clone of p53-mutated keratinocytes in normal human skin. Brash, D.E. and Leffell, D. Sunlight and skin cancer. Jonason, A. S., Kunala, S., Price, G. J., Restifo, R. J., Spinelli, H. M., Persing, J. A., Leffell, D. J., Tarone, R. E., and Brash, D. E. Frequent clones of p53-mutated keratinocytes in normal human skin. Brash, D. E. Sunlight and the onset of skin cancer.