Moriwaki S I, Tarone R E, Tucker M A, Goldstein A M, Kraemer K H
Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Res. 1997 Oct 15;57(20):4637-41.
Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk of developing CM. Using a shuttle vector plasmid, pSP189, cell lines from three patients with CM plus DN were previously found to have elevated post-UV plasmid mutability. To investigate familial 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 elevated 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 only (P = 0.001). Elevated spontaneous plasmid mutation frequency (MF) was 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 lines from two patients with CM without DN had normal post-UV plasmid MF. Although not specific for CM patients, of 27 cell lines with elevated post-UV plasmid MF, only 8 were from donors who did not have CM + DN or DN (19 of 24 versus 8 of 28; P = 0.0003). This study indicates that 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.
患有发育异常痣（DN）的皮肤黑色素瘤（CM）家族成员患CM的风险很高。使用穿梭载体质粒pSP189，先前发现来自三名CM加DN患者的细胞系在紫外线照射后的质粒突变率升高。为了研究这种细胞表型的家族性发生情况，我们检测了来自6个家族性CM家系的31个淋巴母细胞系紫外线照射后的质粒突变率。与16个正常对照系相比，我们发现来自13名CM加DN患者中的13人（P = 1.5×10^(-8)）以及8名仅患有DN患者中的5人（P = 0.001）的细胞系紫外线照射后的质粒突变率异常升高。6名CM加DN患者（P = 0.002）和3名仅患有DN患者（P = 0.028）的细胞系中也存在自发质粒突变频率（MF）升高的情况。然而，来自两名无DN的CM患者的细胞系紫外线照射后的质粒MF正常。虽然对CM患者不具有特异性，但在27个紫外线照射后质粒MF升高的细胞系中，只有8个来自没有CM + DN或DN的供体（24个中的19个与28个中的8个；P = 0.0003）。这项研究表明，紫外线照射后质粒高突变性是黑色素瘤易感家族成员的实验室标志物，并提示家族性CM患者处理紫外线诱导的DNA损伤的机制存在缺陷。
