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Discovering the causes of cancer and the means of prevention

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Title: Frequent clones of p53-mutated keratinocytes in normal human skin.
Authors: Jonason AS,  Kunala S,  Price GJ,  Restifo RJ,  Spinelli HM,  Persing JA,  Leffell DJ,  Tarone RE,  Brash DE
Journal: Proc Natl Acad Sci U S A
Date: 1996 Nov 26
Branches: BB
PubMed ID: 8943054
PMC ID: PMC19488
Abstract: 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 40 cells per cm2 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 cancer.