Ping X L, Ratner D, Zhang H, Wu X L, Zhang M J, Chen F F, Silvers D N, Peacocke M, Tsou H C
Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
J Invest Dermatol. 2001 Apr;116(4):614-6. doi: 10.1046/j.1523-1747.2001.01301.x.
Ultraviolet light exposure is the major risk factor for the development of squamous cell carcinoma in Caucasians. Mutations in the tumor suppressor gene p53 have been identified in both squamous cell carcinomas and basal cell carcinomas. The human homolog of the Drosophila patched gene, has been shown to be mutated in sporadic basal cell carcinomas; however, mutations in the patched gene have not been found in squamous cell carcinoma. In this study, we screened a total of 20 squamous cell carcinoma samples for mutations in the patched gene. Using polymerase chain reaction-single strand conformation polymorphism as an initial screening method, we identified one non-sense mutation, two mis-sense mutations and three silent mutations in five squamous cell carcinoma samples. In one squamous cell carcinoma sample, we identified a tandem GG-->AA transitional change at nucleotide 3152 in exon 18 of the patched gene that resulted in a premature stop codon at codon 1051. The three squamous cell carcinoma samples containing non-sense and mis-sense mutations were isolated from individuals with histories of multiple basal cell carcinoma. Sequence analysis of the p53 gene in these five squamous cell carcinoma samples identified one CC-->TT and three C-->T ultraviolet-specific nucleotide changes. Our study provides evidence that the patched gene is mutated in squamous cell carcinoma from individuals with a history of multiple basal cell carcinoma. The identification of ultraviolet-specific nucleotide changes in both tumor suppressor genes supports the notion that ultraviolet exposure plays an important part in the development of squamous cell carcinoma.
紫外线照射是白种人发生鳞状细胞癌的主要风险因素。在鳞状细胞癌和基底细胞癌中均已发现肿瘤抑制基因p53发生突变。果蝇patched基因的人类同源基因，已被证实在散发性基底细胞癌中发生突变；然而，在鳞状细胞癌中尚未发现patched基因发生突变。在本研究中，我们对总共20个鳞状细胞癌样本进行了patched基因突变筛查。使用聚合酶链反应-单链构象多态性作为初始筛查方法，我们在5个鳞状细胞癌样本中鉴定出1个无义突变、2个错义突变和3个沉默突变。在1个鳞状细胞癌样本中，我们在patched基因第18外显子的核苷酸3152处鉴定出一个串联的GG→AA转换变化，该变化导致密码子1051处出现提前终止密码子。这3个含有无义突变和错义突变的鳞状细胞癌样本是从有多个基底细胞癌病史的个体中分离出来的。对这5个鳞状细胞癌样本中的p53基因进行序列分析，鉴定出1个CC→TT和3个C→T紫外线特异性核苷酸变化。我们的研究提供了证据，表明patched基因在有多个基底细胞癌病史个体的鳞状细胞癌中发生突变。在两个肿瘤抑制基因中均鉴定出紫外线特异性核苷酸变化，支持了紫外线照射在鳞状细胞癌发生中起重要作用这一观点。
