Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.

Correspondence: Dr Norbert M Wikonkal, Yale University School of Medicine Radiobiology Laboratories, 333 Cedar Street P.O. Box 208040, New Haven, CT 06520-8040. E-mail: norbert.wikonkal@yale.edu

Received 14 July 1999; Accepted 15 July 1999.

Abstract

The photons of sunlight begin a series of genetic events in skin leading to cancer. UV signature mutations provide an alternative to inherited mutations as a way of identifying genes that are involved in cancer development. They augment epidemiologic and clinical data by serving as molecular evidence for the role of UV radiation in skin carcinogenesis. Signature mutations are present in TP53 and PTCH, two tumor suppressor genes responsible for non-melanoma skin cancer. We review evidence that clones of TP53-mutated cells are present in normal human and murine epidermis exposed to UVB and conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of TP53 mutated cells. These combined actions of sunlight result in normal individuals' carrying a substantial burden of keratinocytes predisposed to cancer. Thus cancer involves both a single-cell problem and a multi-cell problem; in skin cancer, sunlight appears to drive both.