Hypermutability of UV-treated Plasmids in Dysplastic Nevus/Familial Melanoma Cell Lines

摘要: Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk developing CM. Using a shuttle vector plasmid, pSP189, cell lines from three patients CM plus DN were previously found to have elevated post-UV plasmid mutability. To investigate familial occurrence this cellular phenotype, we examined mutability in 31 lymphoblastoid 6 kindreds. In comparison 16 normal control lines, an abnormally 13 ( P = 1.5 × 10-8) and 5 8 only 0.001). Elevated spontaneous mutation frequency (MF) was also present six the 0.002) DN-only 0.028). However, two without had MF. Although not specific for patients, 27 MF, donors who did + or (19 24 versus 28; 0.0003). This study indicates that hypermutability is laboratory marker members melanoma-prone suggests defective mechanism handling UV-induced DNA damage.