Frequent clones of p53-mutated keratinocytes in normal human skin

The multiple genetic hit model of cancer predicts that normal individuals 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 keratinocytes, arising from the dermal-epidermal junction and from hair follicles, These clones, 60-3000 cells in size, are present at frequencies 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 being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells, These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to canter.