Mitochondrial DNA copy number changes in human gliomas

Mitochondrial DNA copy number changes in human gliomas
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DOI:
10.1016/0304-3835(96)04276-0
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发表时间:
1996-08-02
期刊:
影响因子:
9.7
通讯作者:
Hays, L
Hays, L
中科院分区:
医学1区
文献类型:
--
作者:
Liang, BC;Hays, L

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基因扩增在肿瘤中具有重要的生物学意义。我们报道了一种利用消减杂交方法获得的互补DNA序列,该序列在人脑胶质瘤中频繁且高度扩增。39/45(87%)的神经胶质肿瘤标本(病理学低级别和高级别)显示该克隆的拷贝数增加5至25倍;在8/45(18%)中发现erb-b扩增。该克隆显示与非连续线粒体DNA位置1679-1948和2017-2057的同源性,其中散布的序列缺失。在克隆的5'端处还存在15个碱基的非线粒体基因组添加和邻近位置1948的7个碱基插入。在11个肿瘤的一个子集中的整个线粒体基因组的评估显示线粒体位置748和5882之间的最大扩增,和其他地方的扩增程度较低,在5/11(46%)的肿瘤中注意到1.2 kb EcoRI片段的复发性缺失。线粒体基因组在人类神经胶质瘤中经常受到影响,需要进一步研究以确定其在神经胶质恶性肿瘤中的作用。
Gene amplification has been found to be biologically important in cancer, We report a complementary DNA sequence obtained using a subtractive hybridization approach which is frequently and highly amplified in human gliomas. 39/45 (87%) glial tumor specimens (of pathologically low and high grade) revealed increases in copy number of this clone from 5- to 25-fold; erb-b amplification was found in 8/45 (18%). This clone revealed homology to non-continuous mitochondrial DNA positions 1679-1948 and 2017-2057, with the interspersed sequences deleted, A non-mitochondrial genomic addition of 15 bases at the 5' end of the clone and a 7 base insertion adjacent: to position 1948 were also present. Evaluation of the entire mitochondrial genome in a subset of 11 tumors showed maximal amplification between mitochondrial positions 748 and 5882, and a lower degree of amplification elsewhere, with a recurrent deletion of a 1.2 kb EcoRI fragment noted in 5/11 (46%) tumors. The mitochondrial genome is frequently affected in human gliomas, and warrants further study to determine its role in glial malignancy.