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 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.
Jonason
A S
AS
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06510, USA.
Kunala
S
S
Price
G J
GJ
Restifo
R J
RJ
Spinelli
H M
HM
Persing
J A
JA
Leffell
D J
DJ
Tarone
R E
RE
Brash
D E
DE
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
D017931:DNA Primers