HYPERMUTABILITY OF UV-TREATED PLASMIDS IN DYSPLASTIC NEVUS FAMILIAL MELANOMA CELL-LINES/

Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk of developing CM. Using a shuttle vector plasmid, pSP 189, cell lints from three patients with CM plus DN were previously fo und to have elevated post-UV plasmid mutability, To investigate famili al occurrence of this cellular phenotype, we examined post-UV plasmid mutability in 31 lymphoblastoid cell lines from 6 familial CM kindreds . In comparison to 16 normal control lines, we found an abnormally ele vated post-UV plasmid mutability in cell lines from 13 of 13 patients with CM plus DN (P = 1.5 x 10(-8)) and from 5 of 8 patients with DN on ly (P = 0.001), Elevated spontaneous plasmid mutation frequency (MF) w as also present in cell lines from six of the CM plus DN patients (P = 0.002) and three of the DN-only patients (P = 0.028), However, cell l ines from two patients with CM without DN had normal post-UV plasmid M F, Although not specific for CM patients, of 27 cell lines with elevat ed post-UV plasmid MF, only 8 were from donors who did not have CM + D N or DN (19 of 24 versus 8 of 28; P = 0.0003), This study indicates th at post-UV plasmid hypermutability is a laboratory marker for members of melanoma-prone families and suggests that patients with familial CM have a defective mechanism for handling UV-induced DNA damage.