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东南亚原发性鼻咽癌中p53基因外显子5的突变聚集情况。

Mutations clustered in exon 5 of the p53 gene in primary nasopharyngeal carcinomas from southeastern Asia.

作者信息

Chakrani F, Armand J P, Lenoir G, Ju L Y, Liang J P, May E, May P

机构信息

Laboratoire d'Oncologie Moléculaire, IRC, IFR du CNRS, Villejuif, France.

出版信息

Int J Cancer. 1995 May 4;61(3):316-20. doi: 10.1002/ijc.2910610307.

Abstract

Mutations in the p53 tumor suppressor gene play an important role in the development of many common human malignancies. In nasopharyngeal carcinomas (NPC), p53 gene mutations were not detected in primary tumors, with one exception for a primary tumor displaying a p53 mutation at codon 280, whereas p53 mutations were identified in some metastatic and nude mouse-passaged NPC specimens. In the present report, 41 NPC primary tumors of the undifferentiated carcinoma nasopharyngeal type (UCNT; 21 from Hong Kong and 20 from Guangxi, southeastern China) were studied. Four point mutations that result in amino acid substitutions were identified by PCR amplification of exons 2-9 and direct DNA sequencing, combined with PCR-single-strand conformation polymorphism analysis. The 4 mutations detected were clustered within the DNA stretch from codon 175 to 177. Our data, taken together with those of others, suggest that mutation in p53 may occur in NPC at various points during tumorigenesis. Alternative mechanisms of p53 inactivation in NPC are also possible.

摘要

p53肿瘤抑制基因的突变在许多常见人类恶性肿瘤的发生发展中起着重要作用。在鼻咽癌(NPC)中,原发性肿瘤未检测到p53基因突变,但有1例原发性肿瘤在密码子280处显示p53突变,而在一些转移性和裸鼠传代的NPC标本中鉴定出p53突变。在本报告中,研究了41例未分化鼻咽癌(UCNT)类型的NPC原发性肿瘤(21例来自香港,20例来自中国东南部广西)。通过对第2至9外显子进行PCR扩增和直接DNA测序,并结合PCR-单链构象多态性分析,鉴定出4个导致氨基酸替换的点突变。检测到的4个突变集中在密码子175至177的DNA片段内。我们的数据与其他研究的数据共同表明,p53突变可能在NPC肿瘤发生的不同阶段出现。NPC中p53失活的其他机制也有可能。

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