FREQUENT CLONES OF P53-MUTATED KERATINOCYTES IN NORMAL HUMAN SKIN

The multiple genetic hit model of cancer predicts that normal individu als should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated kera tinocytes, arising from the dermal-epidermal junction and from hair fo llicles, These clones, 60-3000 cells in size, are present at frequenci es exceeding 10 cells per cm(2) and together involve as much as 4% of the epidermis. in sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin, We conclude that, in addition to bei ng a tumorigenic mutagen, sunlight acts as a tumor promoter by favorin g the clonal expansion of p53-mutated cells, These combined actions of sunlight result in normal individuals carrying a substantial burden o f keratinocytes predisposed to canter.