Takahashi T, Nau M M, Chiba I, Birrer M J, Rosenberg R K, Vinocour M, Levitt M, Pass H, Gazdar A F, Minna J D
National Cancer Institute-Navy Medical Oncology Branch, Bethesda, MD 20814.
Science. 1989 Oct 27;246(4929):491-4. doi: 10.1126/science.2554494.
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 point 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.
等位基因缺失是含有隐性癌基因的染色体区域的一个标志。肺癌常常表现出17号染色体短臂（17p）杂合性缺失。最近的证据表明，位于17p13的p53基因具有这种抗癌基因的许多特征。p53基因在所有类型的人类肺癌中经常发生突变或失活。p53的基因异常包括诸如纯合缺失和大小异常的信使核糖核酸等重大变化，以及各种点突变或小突变，这些突变定位于p53开放阅读框，并在小鼠和人类之间高度保守的区域改变氨基酸序列。此外，与正常肺组织相比，在肺癌细胞系中观察到p53信使核糖核酸表达极低或缺失。这些发现，再加上先前在肺癌中证明的17p等位基因缺失，强烈表明p53是一种抗癌基因，其破坏与人类肺癌的发病机制有关。
