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(American Journal of Pathology. 2001;159:1247-1253.)
© 2001 American Society for Investigative Pathology

Technical Advances

Persistent p53 Mutations in Single Cells from Normal Human Skin

Gao Ling^*, Åsa Persson, Berit Berne, Mathias Uhlén, Joakim Lundeberg and Fredrik Ponten^*

From the Department of Genetics and Pathology,^*
University Hospital, Uppsala; the Department of Dermatology,
Uppsala University, Uppsala; and the Department of Biochemistry and Biotechnology,
Royal Institute of Technology, Stockholm, Sweden

Epidermal clones of p53-mutated keratinocytes are abundant in chronically sun-exposed skin and may play an important role in early development of skin cancer. Advanced laser capture microdissection enables genetic analysis of targeted cells from tissue sections without contamination from neighboring cells. In this study p53 gene mutations were characterized in single cells from normal, chronically sun-exposed skin. Biopsies were obtained from skin subjected to daily summer sun and skin totally protected from the sun by blue denim fabric. Using laser capture microdissection, 172 single-cell samples were retrieved from four biopsies and analyzed using single-cell polymerase chain reaction and direct DNA sequencing. A total of 14 different mutations were identified in 26 of 99 keratinocytes from which the p53 gene could be amplified. Mutations displayed a typical UV signature and were detected in both scattered keratinocytes and in a small cluster of p53-immunoreactive keratinocytes. This minute epidermal p53 clone had a diameter of 10 to 15 basal cells. Two missense mutations were found in all layers of epidermis within the p53 clone. The presented data show that p53 mutations are common in normal skin and that a clone of keratinocytes with a mutated p53 gene prevailed despite 2 months of total protection from ultraviolet light.

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