Frequent clones of p53-mutated keratinocytes in normal human skin
AS Jonason, S Kunala, GJ Price… - Proceedings of the …, 1996 - National Acad Sciences
AS Jonason, S Kunala, GJ Price, RJ Restifo, HM Spinelli, JA Persing, DJ Leffell, RE Tarone…
Proceedings of the National Academy of Sciences, 1996•National Acad SciencesThe 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 …
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 …
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.
National Acad Sciences