Abstract
Keratinocytes in the epidermis are exposed to sun light, inducing DNA damage such as cyclobutane pyrimidine dimmers and (6-4)photoproducts. In patients with xeroderma pigmentosum, the nucleotide excision repair, which plays a role in DV induced DNA damage, is disrupted. Thus, we speculate the mechanism of UV carcinogenesis observing the skin cancer in XP patients and non-XP patients.
Gene alterations of RAS and p53 mutations in skin cancers from XP patients are summarized from our data and others. We concluded that the sun exposure causes the mutations in the oncogene and tumor suppressor genes, and another important aspect is where these mutations occur. In case sites of RAS mutations are not colon 12, 13, 61, which causes the activation of oncogene, the transforming activity is very low, though the mutations are detected elsewhere.
Gene alterations detected are predominantly transition type at the dipyrimidine sites both in melanoma and non-melanoma skin cancers observed in XP patients. Gene alterations of non-melanoma skin cancer in sun exposed areas in non-XP patients are also predominated by the transition type mutations at the dipyrimidine sites. [Skin Cancer (Japan) 2003; 18: 137-146]
