Ultraviolet-induced p53 mutations in atypical fibroxanthoma.
Atypical fibroxanthoma (AFX) is an uncommon neoplasm of the superficial soft tissue occurring in actinically damaged skin of elderly patients. Sun-exposed skin also represents the main site of squamous and basal cell carcinomas and malignant melanoma, and a key role for ultraviolet (UV) radiation in their pathogenesis has long been suspected. UV-related mutations of the p53 gene have been identified in human skin cancers. To verify whether the pathogenesis of AFX is related to the effect of sunlight, p53 protein and gene status have been investigated in a series of 10 cases of AFX. Seven of 10 showed p53 immunoreactivity in most of the neoplastic cells. Molecular analysis of the p53 gene revealed an abnormal single strand conformation polymorphism pattern in all the p53 positive cases. Polymerase chain reaction direct sequencing revealed that all the mutations involved cytosine bases. Four cases showed C to T transitions (including two CC-TT double base substitutions) and two cases showed C to G transversion. All but one mutation took place at dipyrimidine sites. These findings provide the first objective evidence for the central role of UV radiation in the development of AFX and also represent the first in vivo demonstration of solar UV-induced mutations in a human mesenchymal neoplasm.
Department of Histopathology, City Hospital, Feltre, Italy.
A P
AP
Dei Tos
R
R
Maestro
C
C
Doglioni
D
D
Gasparotto
M
M
Boiocchi
L
L
Laurino
C D
CD
Fletcher
D001483:Base Sequence; D016158:Genes, p53 / Q000235:genetics* / Q000528:radiation effects; D018219:Histiocytoma, Benign Fibrous / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*