Identification of intronic point mutations as an alternative mechanism for p53 inactivation in lung cancer.
Identification of intronic point mutations as an alternative mechanism for p53 inactivation in lung cancer.
复制标题
鉴定内含子点突变作为肺癌 p53 失活的替代机制。
DOI：
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发表时间：
1990
影响因子：
15.9
通讯作者：
John D. Minna
中科院分区：
文献类型：
--
作者：
Takashi Takahashi;D. D'Amico;Itsuo Chiba;D. Buchhagen;John D. Minna
p53基因最初被认为是一种癌基因，但最近的证据表明，野生型p53可以作为一种肿瘤抑制基因在肺癌，结肠癌，乳腺癌以及不太常见的恶性肿瘤。本研究报告的第一个确定的内含子点突变的p53肿瘤抑制基因的失活机制。在小细胞和非小细胞肺癌细胞系中发现的异常大小的p53 mRNA的特征在于通过cDNA/PCR产物的序列分析，RNA酶保护试验和免疫沉淀。发现这些mRNA代表异常剪接，导致产生异常或不产生p53蛋白。基因组DNA的序列分析表明，在第三内含子的剪接受体位点或剪接供体位点的第七内含子的点突变占异常mRNA剪接。在一名患者中，相同的内含子点突变被发现在肿瘤细胞系来源于骨髓转移和多发性肝转移，但不是在正常的DNA，这表明它发生作为一个体细胞事件之前，这些转移的发展。这些发现进一步支持了p53基因失活在肺癌发病机制中的作用，并表明内含子点突变在这一过程中的作用。
The p53 gene initially was thought to be an oncogene, but recent evidence suggests that wild-type p53 can function as a tumor suppressor gene in lung, colon, and breast cancer as well as less common malignancies. This study reports the first identification of intronic point mutations as a mechanism for inactivation of the p53 tumor suppressor gene. Abnormally sized p53 mRNAs found in a small cell and a non-small cell lung cancer cell line were characterized by sequence analysis of cDNA/PCR products, the RNase protection assay and immunoprecipitation. These mRNAs were found to represent aberrant splicing leading to the production of abnormal or no p53 protein. Sequence analysis of genomic DNA revealed that a point mutation at the splice acceptor site in the third intron or the splice donor site in the seventh intron accounts for the abnormal mRNA splicing. In one patient the same intronic point mutation was found in the tumor cell line derived from a bone marrow metastasis and in multiple liver metastases but not in normal DNA, indicating that it occurred as a somatic event before the development of these metastases. These findings further support the role of inactivation of the p53 gene in the pathogenesis of lung cancer and indicate the role of intronic point mutation in this process.
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DOI：
10.1056/nejm198912213212501
发表时间：
1989-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
D. Yandell;T. Campbell;Siri H. Dayton;R. Petersen;David Walton;J. Little;Allyn McConkie-Rosell;E. Buckley;T. Dryja
通讯作者：
D. Yandell;T. Campbell;Siri H. Dayton;R. Petersen;David Walton;J. Little;Allyn McConkie-Rosell;E. Buckley;T. Dryja
DOI：
10.1073/pnas.87.7.2775
发表时间：
1990-04-01
影响因子：
11.1
作者：
HOROWITZ, JM;PARK, SH;WEINBERG, RA
通讯作者：
WEINBERG, RA
影响因子：
56.9
作者：
HOROWITZ, JM;YANDELL, DW;DRYJA, TP
通讯作者：
DRYJA, TP
影响因子：
56.9
作者：
BAKER, SJ;FEARON, ER;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1073/pnas.84.21.7716
发表时间：
1987-11-01
影响因子：
11.1
作者：
MASUDA, H;MILLER, C;CLINE, MJ
通讯作者：
CLINE, MJ