Frequent clones of p53-mutated keratinocytes in normal human skin

Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14025-9. doi: 10.1073/pnas.93.24.14025.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Cells, Cultured
  • DNA Primers
  • Epidermal Cells
  • Epidermis / metabolism
  • Genes, p53*
  • Hair / cytology
  • Hair / metabolism
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Microscopy, Confocal
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Skin / cytology
  • Skin / metabolism*
  • Sunlight

Substances

  • DNA Primers