Spencer J M, Kahn S M, Jiang W, DeLeo V A, Weinstein I B
Department of Dermatology, Columbia University, New York, NY, USA.
Arch Dermatol. 1995 Jul;131(7):796-800.
BACKGROUND/DESIGN: The clonal theory of cancer predicts that transformed cells within a given tumor are derived from a single initiated precursor. Advancement of this precursor through various stages of tumor development occurs with the further accumulation of selective genetic and epigenetic lesions. Mammalian ras genes are important constituents of mitogenic signaling pathways, and when activated, they contribute to deregulated cellular growth. Activated ras genes play important roles in the development of certain skin tumors. Studies on a number of animal tumor model systems have shown that ras gene activation can be an early and perhaps initial event in the development of skin tumors. Activated ras genes are also found in a significant percentage of somatic human squamous cell carcinomas. To gain retrospective insight into the stages at which activated ras genes contribute to squamous cell carcinoma development, we investigated their incidence in actinic keratoses, premalignant precursors to squamous cell carcinomas. Using a nonradioactive polymerase chain reaction-based method developed in our laboratory, we examined a panel of 19 actinic keratoses and 33 squamous cell carcinomas for activated ras genes.
DNA analysis revealed ras gene mutations in three (16%) of 19 actinic keratoses and in four (12%) of 33 squamous cell carcinomas. Activating mutations occurred at codon 12 of the K-ras gene, and codons 12, 13, and 61 of the H-ras gene. All positive actinic keratoses and squamous cell carcinomas occurred in sun-exposed regions.
Activated ras genes can play important roles during early stages of squamous cell carcinoma development. Aberrant repair of UV-induced pyrimidine dimers is a likely cause of this activation.
背景/设计：癌症的克隆理论预测，给定肿瘤内的转化细胞源自单个起始前体。该前体通过肿瘤发展的各个阶段的进展伴随着选择性遗传和表观遗传损伤的进一步积累。哺乳动物ras基因是有丝分裂原信号通路的重要组成部分，激活后会导致细胞生长失控。激活的ras基因在某些皮肤肿瘤的发展中起重要作用。对多种动物肿瘤模型系统的研究表明，ras基因激活可能是皮肤肿瘤发展中的早期甚至初始事件。在相当比例的人类体细胞鳞状细胞癌中也发现了激活的ras基因。为了回顾性地了解激活的ras基因在鳞状细胞癌发展的哪些阶段起作用，我们研究了它们在光化性角化病（鳞状细胞癌的癌前前体）中的发生率。我们使用在我们实验室开发的基于非放射性聚合酶链反应的方法，检测了一组19个光化性角化病和33个鳞状细胞癌中的激活ras基因。
DNA分析显示，19个光化性角化病中有3个（16%）和33个鳞状细胞癌中有4个（12%）存在ras基因突变。激活突变发生在K-ras基因的第12密码子以及H-ras基因的第12、13和61密码子。所有阳性的光化性角化病和鳞状细胞癌均发生在阳光暴露部位。
激活的ras基因在鳞状细胞癌发展的早期阶段可能起重要作用。紫外线诱导的嘧啶二聚体的异常修复可能是这种激活的原因。
