P53 - A FREQUENT TARGET FOR GENETIC ABNORMALITIES IN LUNG-CANCER
P53 - A FREQUENT TARGET FOR GENETIC ABNORMALITIES IN LUNG-CANCER
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DOI：
10.1126/science.2554494
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发表时间：
1989-10-27
期刊：
影响因子：
56.9
通讯作者：
MINNA, JD
中科院分区：
文献类型：
--
作者：
TAKAHASHI, T;NAU, MM;MINNA, JD
等位基因丢失是隐藏隐性癌基因的染色体区域的标志。肺癌常表现为17p杂合性缺失。最近的证据表明，位于17p13上的p53基因具有这种反基因的许多特征。p53基因在所有类型的人类肺癌中经常发生突变或失活。p53的遗传异常包括纯合缺失和大小异常的信使rna等重大变化，以及各种微小的突变，这些突变映射到p53的开放阅读框，并改变了小鼠和人类之间高度保守区域的氨基酸序列。此外，与正常肺相比，肺癌细胞系中p53信使RNA的表达非常低或缺失。这些发现，加上先前在肺癌中发现的17p等位基因缺失，强烈暗示p53是一种抗癌基因，其破坏参与了人类肺癌的发病机制。
Allele loss is a hallmark of chromosome regions harboring recessive oncogenes. Lung cancer frequently demonstrates loss of heterozygosity on 17p. Recent evidence suggests that the p53 gene located on 17p13 has many features of such an antioncogene. The p53 gene was frequently mutated or inactivated in all types of human lung cancer. The genetic abnormalities of p53 include gross changes such as homozygous deletions and abnormally sized messenger RNAs along with a variety of pint or small mutations, which map to the p53 open reading frame and change amino acid sequence in a region highly conserved between mouse and man. In addition, very low or absent expression of p53 messenger RNA in lung cancer cell lines compared to normal lung was seen. These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.