Melanoma and Other Skin Cancers in Xeroderma Pigmentosum Patients and Mutation in Their Cells

Abstract

Malignant melanomas were found in 15.8% of xeroderma pigmentosum (XP) patients with skin cancer in Japan. When multiple cancers were scored separately depending on the histopathologic types, 12.1% of the skin cancers in XP patients was malignant malignant melanoma. The relative incidence of malignant melanoma in skin cancer in XP patients is similar to that in skin cancer in general (12.6%), reported previously. Most of the malignant melanoma in XP patients developed in skin exposed to sunlight, in contrast to the high incidence of malignant melanoma in general in the unexposed skin of Japanese people. A DNA repair defect of UV damage is strongly suggested to be responsible for the high incidence of skin cancer in XP patients. The onset of malignant melanoma in XP patients was about ten years old, and was as early as those of basal cell carcinoma and squamous cell carcinoma in the patients with very low DNA repair capacities. Among nine genetic complementation groups and a variant type, group A XP cells were found to be extremely hypermutable by ultraviolet light, while group C XP cells were also hypermutable, but at the same level as normal cells when adjusted for survival. Mutagenesis as a possible mechanism of carcinogenesis in XP is supported by these results, but evidence in other cancer-prone hereditary diseases is yet to be obtained.