TRANSFORMING RAS GENES FROM HUMAN-MELANOMA - A MANIFESTATION OF TUMOR HETEROGENEITY
TRANSFORMING RAS GENES FROM HUMAN-MELANOMA - A MANIFESTATION OF TUMOR HETEROGENEITY
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DOI：
10.1038/308069a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
OLD, LJ
中科院分区：
文献类型：
--
作者：
ALBINO, AP;LESTRANGE, R;OLD, LJ
构成个体肿瘤的细胞表型的变异性是动物和人类癌症的显著特征，通常称为肿瘤异质性1。对来自肿瘤的克隆衍生细胞群的研究表明，肿瘤由多种性状不同的细胞组成，包括耐药性、抗原表达和转移潜力2 -6。肿瘤异质性的起源和维持尚不清楚，但突变和表观遗传机制被认为参与其中。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，这些结果提出了ras基因激活遵循与肿瘤异质性相关的其他特征相同的可变模式的可能性。在NIH/3 T3检测中，30个黑素瘤细胞系中有4个的DNA产生了转化基因。在来自单个患者的单独转移性沉积物的五个细胞系中，只有一个含有激活的ras，表明在这种情况下ras激活的异质性，并表明ras激活不参与该患者的肿瘤起始或维持。
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 heterogeneity1. 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 potential2–6. 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 thatrasgene activation follows the same variable pattern as other traits involved in tumour heterogeneity. DNA from 4 of 30 melanoma cell lines yielded transformingrasgenes in the NIH/3T3 assay. Of five cell lines originating from separate metastatic deposits of a single patient, only one contained activatedras, indicating heterogeneity inrasactivation in this case and suggesting thatrasactivation was not involved in tumour initiation or maintenance in this patient.