Albino A P, Le Strange R, Oliff A I, Furth M E, Old L J
Nature. 1984;308(5954):69-72. doi: 10.1038/308069a0.
Variability in the phenotype of cells comprising individual tumours is a striking feature of animal and human cancer and is generally referred to as tumour heterogeneity. Studies of clonally derived cell populations from tumours that originated presumably from a single transformed cell have shown that tumours are made up of cells that differ in a variety of traits, including drug resistance, antigen expression and metastatic potential. The origin and maintenance of tumour heterogeneity are unclear, but mutational and epigenetic mechanisms are thought to be involved. Here we report the results of a search for transforming genes in human melanoma which have raised the possibility that ras gene activation follows the same variable pattern as other traits involved in tumour heterogeneity. DNA from 4 of 30 melanoma cell lines yielded transforming ras genes in the NIH/3T3 assay. Of five cell lines originating from separate metastatic deposits of a single patient, only one contained activated ras, indicating heterogeneity in ras activation in this case and suggesting that ras activation was not involved in tumour initiation or maintenance in this patient.
构成单个肿瘤的细胞表型的变异性是动物和人类癌症的一个显著特征，通常被称为肿瘤异质性。对可能源自单个转化细胞的肿瘤的克隆衍生细胞群体的研究表明，肿瘤是由在多种特征上存在差异的细胞组成的，这些特征包括耐药性、抗原表达和转移潜能。肿瘤异质性的起源和维持尚不清楚，但认为涉及突变和表观遗传机制。在这里，我们报告了在人类黑色素瘤中寻找转化基因的结果，这增加了ras基因激活遵循与肿瘤异质性中其他特征相同的可变模式的可能性。在NIH/3T3检测中，30个黑色素瘤细胞系中的4个细胞系的DNA产生了转化性ras基因。在源自一名患者的不同转移灶的五个细胞系中，只有一个含有激活的ras，这表明在这种情况下ras激活存在异质性，并表明ras激活与该患者肿瘤的起始或维持无关。
