INCREASED EXPRESSION OF MUTANT FORMS OF P53 ONCOGENE IN PRIMARY LUNG-CANCER

INCREASED EXPRESSION OF MUTANT FORMS OF P53 ONCOGENE IN PRIMARY LUNG-CANCER
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DOI:
10.1016/0140-6736(90)90801-b
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发表时间:
1990-03-24
期刊:
影响因子:
168.9
通讯作者:
HARRIS, AL
HARRIS, AL
中科院分区:
医学1区
文献类型:
--
作者:
IGGO, R;GATTER, K;HARRIS, AL

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主要组织学类型的原发性肺癌样品通过免疫组织化学检测肿瘤抑制基因p53的表达。40例肺癌中有28例p53表达异常,17例鳞癌中有14例p53表达异常,而7例类癌和10例正常肺组织中均未检测到p53表达。通过不对称聚合酶链反应mRNA测序策略获得了代表性癌中突变型p53 mRNA纯合表达的直接证据,该策略允许无需任何克隆步骤的测序。所有的突变都是G到T的颠换,导致在进化中高度保守的氨基酸的错义突变。p53基因突变是人类肺癌中最常见的遗传变化,这些发现表明,简单的免疫组织学方法可以提供这种突变的有力证据。
Primary lung cancer samples of the major histological types were examined for expression of the tumour suppressor gene p53 by immunohistochemistry. Abnormalities in p53 expression were found in 28 of 40 carcinomas, 14 of 17 squamous tumours showing abnormal p53 expression, whereas no expression of p53 was detectable in 7 carcinoid tumours or in 10 normal lung samples. Direct evidence for homozygous expression of mutant p53 mRNA in representative carcinomas was obtained by means of an asymmetric polymerase chain reaction mRNA sequencing strategy, which allowed sequencing without any cloning step. All the mutations were G to T transversions resulting in mis-sense mutations in aminoacids highly conserved in evolution. Mutation of the p53 gene is the most frequently identified genetic change in human lung cancer; these findings suggest that simple immunohistological methods can provide strong evidence of such mutation.