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PMID: 8943054 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Frequent clones of p53-mutated keratinocytes in normal human skin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 24 ·1996-11-26 ·Pages 14025-9

Jonason AS, Kunala S, Price GJ, Restifo RJ, Spinelli HM, Persing JA, Leffell DJ, Tarone RE, Brash DE

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.

MeSH Terms
Adult Aged Cells, Cultured DNA Primers Epidermal Cells Epidermis/metabolism Genes, p53 Hair/cytology,metabolism Humans Keratinocytes/cytology,metabolism Microscopy, Confocal Middle Aged Mutation Polymerase Chain Reaction Skin/cytology,metabolism Sunlight
Chemicals
DNA Primers
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Jonason A S
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06510, USA.
Kunala S
Price G J
Restifo R J
Spinelli H M
Persing J A
Leffell D J
Tarone R E
Brash D E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.24.14025
Published
1996-11-26
Pages
14025-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19488
Subset
IM
Grants
NCI NIH HHS · R01 CA055737 · United States
NCI NIH HHS · CA55737 · United States
Corrections
CommentIn
PMID: 8990152
External Links
PubMed source DOI: 10.1073/pnas.93.24.14025 PMC Full Text View journal details
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