Campbell C, Quinn A G, Rees J L
University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K.
Br J Dermatol. 1993 Feb;128(2):111-4. doi: 10.1111/j.1365-2133.1993.tb15137.x.
ras mutations have been reported as an early event in some human malignancies and in the mouse skin model of multistep carcinogenesis; early studies in human non-melanoma skin cancers have reported variable rates of ras mutations. A recent study, however, has reported a high frequency of activating mutations of the Harvey-ras proto-oncogene in non-melanoma skin cancers, and the site specificity of the mutation at the second position of codon 12 prompted us to re-examine the importance of Ha-ras codon 12 mutations as an early event in the development of these tumours, using a combination of PCR and restriction fragment polymorphism of codon 12 of the Ha-ras gene. Dilution experiments confirmed that the method was sensitive and capable of detecting mutations at this codon when only 4% of the total alleles are mutated. We were surprised to find no mutations in the 40 basal cell carcinomas, 12 squamous cell carcinomas and 12 cases of Bowen's disease studied. We conclude that Ha-ras codon 12 mutations are rare events in human non-melanoma skin cancer in the U.K. The marked differences in the frequency of codon 12 Ha-ras mutations in published studies may relate to either technical artefacts, or differences in the molecular epidemiology between areas of low and high sun exposure.
Ras突变在一些人类恶性肿瘤以及多步骤致癌的小鼠皮肤模型中被报道为早期事件；早期对人类非黑色素瘤皮肤癌的研究报道了Ras突变的不同发生率。然而，最近一项研究报道了在非黑色素瘤皮肤癌中Harvey-ras原癌基因激活突变的高频率，并且密码子12第二位的突变位点特异性促使我们使用PCR和Ha-ras基因密码子12的限制性片段多态性相结合的方法，重新审视Ha-ras密码子12突变作为这些肿瘤发生早期事件的重要性。稀释实验证实，当仅4%的总等位基因发生突变时，该方法灵敏且能够检测到该密码子处的突变。我们惊讶地发现在所研究的40例基底细胞癌、12例鳞状细胞癌和12例鲍恩病中均未发现突变。我们得出结论，在英国，Ha-ras密码子12突变在人类非黑色素瘤皮肤癌中是罕见事件。已发表研究中密码子12 Ha-ras突变频率的显著差异可能与技术假象或低日照和高日照地区之间分子流行病学的差异有关。
