Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma.
Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma.
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DOI：
10.1186/1755-8794-4-60
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发表时间：
2011-07-19
影响因子：
2.7
通讯作者：
Jin W
中科院分区：
文献类型：
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作者：
Dong H;Zhang H;Liang J;Yan H;Chen Y;Shen Y;Kong Y;Wang S;Zhao G;Jin W
肝细胞癌（Hepatocellular carcinoma，HCC）是一种世界性的肝脏恶性肿瘤，在我国发病率较高.亚染色体扩增和缺失占主要的基因组变异发生在HCC。数字化核型分析是一种高分辨率分析全基因组染色体畸变的有效方法。构建了肝癌数字化核型文库，并应用罗氏公司的454基因组测序仪FLX系统对文库进行了大规模测序。使用Digital Karyotyping Data Viewer软件分析基因组扩增和缺失。通过实时定量PCR检测通过数字核型分析检测的基因的基因组扩增。采用实时荧光定量RT-PCR方法检测癌组织和癌旁组织中这些基因的mRNA表达水平。从肝癌数字核型库中共获得821，252个基因组标签，其中529，162个标签（64%）映射到人类基因组的独特位点。通过对数字化核型分析数据的分析，发现了多个亚染色体扩增和缺失，其中7q21.3的扩增引起了我们的特别关注。对7q21.3位点扩增子内的基因进行验证，发现SGCE、PEG 10、DYNC 1 I1和SLC 25 A13的基因组扩增分别发生在52例HCC标本中的11例（21%）、11例（21%）、11例（21%）和23例（44%）。此外，SGCE，PEG 10和DYNC 1 I1的mRNA表达水平显着上调，在肿瘤肝组织与相应的非肿瘤对应。我们的结果表明，7q21.3亚染色体区域在HCC中扩增，SGCE，PEG 10和DYNC 1 I1可能是位于7q21.3位点的原癌基因。
Hepatocellular carcinoma (HCC) is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution. A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche) was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR. A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64%) mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%), 11 (21%), 11 (21%) and 23 (44%) of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts. Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus.
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影响因子：
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作者：
Igarashi, Akira;Segoshi, Kazumi;Kato, Yukio
通讯作者：
Kato, Yukio
影响因子：
13.5
作者：
Kusano, N;Shiraishi, K;Sasaki, K
通讯作者：
Sasaki, K
影响因子：
13.5
作者：
BOIX, L;ROSA, JL;BARTRONS, R
通讯作者：
BARTRONS, R
影响因子：
14.8
作者：
Leary, Rebecca J.;Cummins, Jordan;Velculescu, Victor E.
通讯作者：
Velculescu, Victor E.
DOI：
10.1038/nrm2804
发表时间：
2009-12
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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