Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype.
Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype.
复制标题
DOI：
--
复制
发表时间：
1989
期刊：
影响因子：
8
通讯作者：
A. P. Albino;D. M. Nanus;I. R. Mentle;Carlos Cordon-Cardo;N. McNutt;Jan Bressler;Michael Andreeff
中科院分区：
文献类型：
--
作者：
A. P. Albino;D. M. Nanus;I. R. Mentle;Carlos Cordon-Cardo;N. McNutt;Jan Bressler;Michael Andreeff
本研究检查了非培养和培养黑色素瘤和相关前体标本的 (i) 使用聚合酶链式反应 (PCR) 方法的突变 ras 基因，(ii) 突变 ras 基因与分化相关表型特征的相关性，(iii) 通过免疫过氧化物酶分析组织中 ras 编码的 p21 蛋白的表达，(iv) 通过流式细胞术定量表达突变型和野生型 ras 编码的 p21 蛋白，以及 (v) 之间的相关性p21 表达、ras 突变的发生和细胞周期动力学。这些研究的结果是（1）24%的培养的恶性黑色素瘤具有激活的ras基因，其中N-ras的激活频率是Harvey（Ha）-ras的十倍。每个激活 ras 基因的例子都显示出蛋白质第 61 个密码子处的突变，但一个黑色素瘤除外，它显示出 N-ras 基因第 13 号密码子处的突变； (2) 所有表现出激活的 ras 基因的黑色素瘤都具有相似的细胞表面表型，并且似乎来自相似的分化阶段； (3) 5-6%的非培养原发性和转移性黑色素瘤具有ras基因突变； (4)任何前驱病变，特别是正常痣和发育异常痣均未发现ras基因突变； (5) 石蜡包埋标本的免疫过氧化物酶分析表明 p21 表达没有与肿瘤进展相关的定量或定性变化； (6)指数生长或平台期黑色素瘤细胞之间，以及有或没有ras突变的黑色素瘤细胞之间p21表达没有明显差异；在有和没有突变ras基因的细胞之间也没有发现任何细胞动力学差异。这些研究表明，ras 突变的作用可能仅限于间接参与黑色素瘤子集的转化。
This study examined noncultured and cultured melanomas and related precursor specimens for (i) mutated ras genes using polymerase chain reaction (PCR) methodology, (ii) correlation of mutated ras genes with differentiation related phenotypic characteristics, (iii) expression of ras-encoded p21 proteins in tissues by immunoperoxidase analysis, (iv) quantitative expression of mutated and wild-type ras encoded p21 proteins by flow cytometry, and (v) correlation between p21 expression, the occurrence of ras mutations, and cell cycle kinetics. The results of these studies are (1) 24% of cultured malignant melanomas have activated ras genes, with N-ras being activated ten times as frequently as Harvey (Ha)-ras. Each example of an activated ras gene showed a mutation at the 61st codon of the protein, with the exception of one melanoma which showed a mutation at codon 13 of the N-ras gene; (2) all the melanomas displaying an activated ras gene had a similar cell surface phenotype and appear to come from a similar phase of differentiation; (3) 5-6% of noncultured primary and metastatic melanomas have mutated ras genes; (4) no ras gene mutations were found in any precursor lesion, specifically normal nevi and dysplastic nevi; (5) immunoperoxidase analysis of paraffin-embedded specimens indicated no quantitative or qualitative alterations in p21 expression that correlate with tumor progression; (6) there were no observable differences in p21 expression between melanoma cells growing exponentially or in plateau phase, or between melanoma cells with or without ras mutations; nor were any cell kinetic differences found between cells with and without mutated ras genes. These studies suggest that the role of ras mutations may be limited to an indirect involvement in the transformation of a subset of melanomas.