SELECTIVE G-MUTATION TO T-MUTATION OF P53 GENE IN HEPATOCELLULAR-CARCINOMA FROM SOUTHERN AFRICA
SELECTIVE G-MUTATION TO T-MUTATION OF P53 GENE IN HEPATOCELLULAR-CARCINOMA FROM SOUTHERN AFRICA
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DOI：
10.1038/350429a0
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发表时间：
1991-04-04
期刊：
影响因子：
64.8
通讯作者：
OZTURK, M
中科院分区：
文献类型：
--
作者：
BRESSAC, B;KEW, M;OZTURK, M
肝细胞癌是撒哈拉以南非洲和东亚的一种常见癌症1。乙肝病毒和黄曲霉毒素是肝细胞癌的危险因素，但人类肝细胞癌发生的分子机制尚不清楚。3.抑癌基因p53的结构和表达异常在肝癌细胞系4中常见，在中国5号和日本6号中发现了染色体17p的等位基因缺失。本文报告了在南非50%的原发性肝癌中发现的17p等位基因缺失和p53基因突变。在检测到的五个突变中，有四个是G-->；T替换，并聚集在密码子249。这种突变特异性可以反映特定致癌物的暴露，其中一个候选是黄曲霉毒素B1(参考文献。7)，非洲的一种食品污染物8，它既是一种诱发G到T突变的诱变剂9，也是一种肝脏特异性致癌物10。
HEPATOCELLULAR carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia 1. Hepatitis B virus and aflatoxins are risk factors for HCC 2, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown 3. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines 4, and allelic losses from chromosome 17p have been found in HCCs from China 5 and Japan 6. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G --> T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa 8, which is both a mutagen that induces G to T substitution 9 and a liver-specific carcinogen 10.