D'Errico M, Calcagnile A S, Corona R, Fucci M, Annessi G, Baliva G, Tosti M E, Pasquini P, Dogliotti E
Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanita', Rome, Italy.
Cancer Res. 1997 Feb 15;57(4):747-52.
Tumor DNA from 45 primary basal cell carcinoma (BCC) biopsies was screened for p53 gene mutations, chromosome 9 allele loss, and microsatellite instability. p53 mutation frequency increased significantly as a function of the age at BCC onset ranging from 6% (1/16) in early BCC (before age 40 years) to 35% (10/29) in late BCC. All p53 mutations found implicated sunlight as the mutagen. Chromosome 9 instability (allele loss or microsatellite instability) was detected at high frequency (38%) independently of age at tumor onset. Allelic loss was confined to chromosome 9q, whereas microsatellite instability was observed prevalently on chromosome 9p often in association with a replication error (RER+) phenotype. Most of our late BCC patients reported occupational sun exposure, while early BCC patients recalled childhood (0-20 years) recreational sun exposure. These data suggest that chronic exposure to sunlight is responsible for accumulation of p53 mutations and thus for late BCC appearance, whereas acute UV exposure in childhood and adolescence leads to early skin cancer development in genetically susceptible individuals via a p53-independent pathway.
对45例原发性基底细胞癌（BCC）活检组织的肿瘤DNA进行了p53基因突变、9号染色体等位基因缺失和微卫星不稳定性筛查。p53突变频率随着BCC发病年龄的增加而显著升高，早期BCC（40岁之前）的突变频率为6%（1/16），晚期BCC为35%（10/29）。所有发现的p53突变均表明阳光是诱变剂。9号染色体不稳定性（等位基因缺失或微卫星不稳定性）在高频（38%）时被检测到，与肿瘤发病年龄无关。等位基因缺失局限于9号染色体长臂，而微卫星不稳定性在9号染色体短臂上普遍存在，且常与复制错误（RER+）表型相关。我们的大多数晚期BCC患者报告有职业性阳光暴露，而早期BCC患者回忆起童年（0 - 20岁）有娱乐性阳光暴露。这些数据表明，长期暴露于阳光下会导致p53突变的积累，从而导致晚期BCC的出现，而儿童和青少年时期的急性紫外线暴露会通过一条不依赖p53的途径，导致遗传易感个体早期皮肤癌的发生。
