In vivo somatic mutations in human lymphocytes frequently result from major gene alterations
In vivo somatic mutations in human lymphocytes frequently result from major gene alterations
复制标题
人类淋巴细胞的体内体细胞突变通常是由主要基因改变引起的
DOI：
10.1038/315343a0
复制
发表时间：
1985
期刊：
影响因子：
64.8
通讯作者：
B. Sanderson
中科院分区：
文献类型：
--
作者：
D. Turner;Alexander A. Morley;M. Haliandros;R. Kutlaca;B. Sanderson
体细胞突变，无论是自发的还是由可识别的诱变剂产生的，被认为在癌症的病因学和衰老过程中是重要的。最近，通过染色体X连锁次黄嘌呤磷酸核糖转移酶（HPRT）位点突变的淋巴细胞的计数和克隆扩增技术的发展，使体内人体细胞体细胞突变的研究成为可能1，2。我们研究了人体淋巴细胞hprt基因突变的分子基础，并在此报告了相当高比例（57%）的突变涉及细胞遗传学上不明显的大量基因改变。这些主要的基因改变包括缺失、外显子扩增和Southern分析上的新的、有时扩增的条带。这种变化强调了DNA中信息的流体性质，并可能表明功能性基因丢失参与癌症病因学和衰老稳态失败的一般机制。
Somatic mutations, either spontaneous or produced by identifiable mutagens, are thought to be important in the aetiology of cancer and in the ageing process. The study of somatic mutations in human cells in vivo has recently been made possible by the development of techniques for enumeration and clonal expansion of lymphocytes mutated at the chromosome X-linked hypoxanthine phosphoribosyl transferase (HPRT) locus1,2. We have studied the molecular basis of in vivo hprt mutations in human lymphocytes and report here that a surprisngly high proportion (57%) involve substantial gene alterations which are not evident cytogenetically. These major gene alterations include deletions, exon amplifications and novel, sometimes amplified, bands on Southern analysis. Such changes emphasize the fluid nature of information in DNA and may be indicative of general mechanisms by which functional gene loss is involved in the aetiology of cancer and the homeostatic failure of ageing.