title: Frequent clones of p53-mutated keratinocytes in normal human skin.
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.
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Jonason
authors.forename: S
authors.initials: S
authors.lastname: Kunala
authors.forename: G J
authors.initials: GJ
authors.lastname: Price
authors.forename: R J
authors.initials: RJ
authors.lastname: Restifo
authors.forename: H M
authors.initials: HM
authors.lastname: Spinelli
authors.forename: J A
authors.initials: JA
authors.lastname: Persing
authors.forename: D J
authors.initials: DJ
authors.lastname: Leffell
authors.forename: R E
authors.initials: RE
authors.lastname: Tarone
authors.forename: D E
authors.initials: DE
authors.lastname: Brash
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D017931:DNA Primers; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D016158:Genes, p53; D006197:Hair / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013472:Sunlight
chemical_list: D017931:DNA Primers