Chapter 14 UV radiation, mutations and oncogenic pathways in skin cancer

Abstract

Specific signal transduction pathways that regulate cell cycling, differentiation and apoptosis are found to be corrupted in skin cancers, e.g. the epidermal growth-stimulating Hedgehog pathway in basal cell carcinomas (BCC). Mutations in genes coding for proteins in these pathways lead to persistent disturbances which are passed along to daughter cells, e.g. mutations in the gene for the Patched (PTCH) protein in the Hedgehog pathway. UV radiation damages DNA and can cause such mutations, but thus far only the point mutations in P53 genes from squamous cell carcinomas and BCC, and in PTCH genes from BCC of xeroderma pigmentosum (XP) patients appear to be unambiguously attributable to solar UV radiation. Solar UVB radiation is most effective in causing these point mutations. Other forms of UV-induced genetical changes may, however, contribute to skin carcinogenesis with different wavelength dependencies.