FREQUENCY OF MOLECULAR ALTERATIONS AFFECTING RAS PROTOONCOGENES IN HUMAN URINARY-TRACT TUMORS
FREQUENCY OF MOLECULAR ALTERATIONS AFFECTING RAS PROTOONCOGENES IN HUMAN URINARY-TRACT TUMORS
复制标题
DOI：
10.1073/pnas.82.11.3849
复制
发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
AARONSON, SA
中科院分区：
文献类型：
--
作者：
FUJITA, J;SRIVASTAVA, SK;AARONSON, SA
ras基因家族的成员在许多不同的人类癌症中被激活为癌基因。为了系统地确定这些基因可能参与影响特定靶组织（尿路上皮细胞）的肿瘤过程的频率，通过DNA转染和分子遗传学分析调查了大量ras癌基因的尿路肿瘤。Harvey（Ha）-ras癌基因通过转染在38个肿瘤中的2个中检测到，以生物活性形式进行分子克隆，并且显示在密码子61处含有单碱基变化，导致精氨酸和亮氨酸分别取代该位置的谷氨酰胺。一个额外的Ha-ras癌基因被确定在膀胱癌的限制性多态性密码子12。在21个肿瘤中的1个中，观察到Kirsten（Ki）-ras基因扩增40倍。在所分析的任何肿瘤中均未检测到其他ras基因的扩增。密码子12和61是ras癌基因激活的主要热点。由于基因扩增导致的表达的定量改变可能为原发性人类肿瘤中ras基因的激活提供了另一种机制。
Members of the ras gene family are activated as oncogenes in many different human cancers. To systematically determine the frequency at which such genes might be involved in the neoplastic process affecting a specific target tissue, urothelial cells, a large series of urinary tract tumors for ras oncogenes were surveyed by DNA transfection and molecular genetic analysis. Harvey (Ha)-ras oncogenes were detected in 2 of 38 tumors by transfection, molecularly cloned in biologically active form, and shown to contain single base changes at condon 61 leading to substitutions of arginine and leucine, respectively, for glutamine at this position. One additional Ha-ras oncogene was identified in a bladder carcinoma by restriction polymorphisms at codon 12. In 1 of 21 tumors, a 40-fold amplification of the Kirsten (Ki)-ras gene was observed. No amplification of other ras genes was detected in any of the tumors analyzed. Codons 12 and 61 are the major hot spots of ras oncogene activation. Quantitative alterations in expression due to gene amplification may provide an alternative mechanism for ras gene activation in primary human tumors.