Comparative genomic hybridization array analysis and real-time PCR reveals genomic copy number alteration for lung adenocarcinomas

Comparative genomic hybridization array analysis and real-time PCR reveals genomic copy number alteration for lung adenocarcinomas
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DOI:
10.1007/s00408-006-0009-0
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发表时间:
2006-12-01
期刊:
影响因子:
5
通讯作者:
Lim, Young
Lim, Young
中科院分区:
医学3区
文献类型:
--
作者:
Choi, Jin Soo;Zheng, Long Tai;Lim, Young

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在各种研究中已经观察到肺癌组织中的基因组改变。为分析肺癌患者基因组中的畸变,我们应用阵列比较基因组杂交技术(阵列CGH)对15例肺腺癌(AdC)组织进行了检测。检测染色体区域的拷贝数增加和丢失,并通过实时聚合酶链反应(PCR)确认相应的基因。至于结果,发现了几个经常改变的位点,包括16 p的增加(46%的样本),最常见的丢失在14 q32.33(26%的样本)。在1p、5p、7p、9p、11p、11q、12q、14q、16p、17q、19q、20p、21q和22q处检测到高水平的DNA扩增(> 0.8 log(2)比率)。通过实时PCR检查获得或丢失的基因子集的过度或不足。ECGF 1(22q13.33)、HOXA 9(7p15.2)、MAFG(17q25.3)、TSC 2(16p13.3)和ICAM 1(19p13.2)基因以及16p染色体末端区域(16p13.3pter)的倍数变化程度最高。这些结果表明,微阵列CGH技术可作为肺癌基因组改变的检测工具,上述基因可能成为肺癌发病机制和诊断研究的候选基因。
Genomic alterations in lung cancer tissues have been observed in various studies. To analyze the aberrations in the genome of lung cancer patients, we used array comparative genomic hybridization (array CGH) in 15 lung adenocarcinoma (AdC) tissues. Copy number gains and losses in chromosomal regions were detected and corresponding genes were confirmed by real-time polymerase chain reaction (PCR). As for the results, several frequently altered loci, including gain of 16p (46% of samples), were found, and the most common losses were found in 14q32.33 (26% of samples). High-level DNA amplifications (> 0.8 log(2) ratio) were detected at 1p, 5p, 7p, 9p, 11p, 11q, 12q, 14q, 16p, 17q, 19q, 20p, 21q, and 22q. A subset of genes, gained or lost, was checked for over- or underrepresentation by means of real-time PCR. The degree of fold change was highest in ECGF1 (22q13.33), HOXA9 (7p15.2), MAFG (17q25.3), TSC2 (16p13.3), and ICAM1 (19p13.2) genes and the 16p chromosome terminal region (16p13.3pter). Taken together, these results show that array CGH could be used as a powerful tool for identification of genomic alteration for lung cancer, and the above-mentioned genes may represent potential candidate genes in the study of lung cancer pathogenesis and diagnosis.