Genome-wide analysis of DNA copy number alterations and gene expression in gastric cancer
Genome-wide analysis of DNA copy number alterations and gene expression in gastric cancer
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DOI：
10.1002/path.2424
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发表时间：
2008-12-01
影响因子：
7.3
通讯作者：
Moriyama, M.
中科院分区：
文献类型：
--
作者：
Tsukamoto, Y.;Uchida, T.;Moriyama, M.
基因组拷贝数畸变（CNA）被认为在人类癌症的发展和进展中起主要作用。虽然许多CNA已被报道在胃癌，其全基因组转录的后果知之甚少。在这项研究中，揭示CNAs对胃癌全基因组表达的影响，我们分析了30例胃癌的CNAs阵列比较基因组杂交（阵列CGH）和24这30例的表达谱的阿托伐他汀表达芯片。我们发现，随着激光显微切割的应用，大多数CNA被检测到在更高的频率比以前的研究。值得注意的是，几乎所有病例（97%）都检测到20q13的增加，这表明这可能在胃癌的发病机制中起重要作用。通过比较阵列CGH数据与相同样品的表达谱，我们发现基因组扩增和缺失强烈影响改变的基因组区域中基因的表达。此外，我们确定了125个候选基因，其中114个上调基因位于扩增的复发区域（>10%），11个下调基因位于缺失的复发区域。免疫组化证实了几个候选基因，如CDC 6，SEC 61 G，ANP 32 E，BYSL和FDFT 1的上调。有趣的是，一些候选基因定位于与众所周知的基因如EGFR、ERBB2和SMAD 4相邻的基因组位点，并且一致地通过基因组改变而解除调控。基于这些结果，我们提出我们的候选基因列表可能包含参与进展期胃癌发病机制的新基因。版权所有（C）2008大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Genomic copy number aberrations (CNAs) are believed to play a major role in the development and progression of human cancers. Although many CNAs have been reported in gastric cancer, their genome-wide transcriptional consequences are poorly understood. In this study, to reveal the impact of CNAs on genome-wide expression in gastric cancer, we analysed 30 cases of gastric cancers for their CNAs by array comparative genomic hybridization (array CGH) and 24 of these 30 cases for their expression profiles by oligonucleotide-expression microarray. We found that with the application of laser microdissection, most CNAs were detected at higher frequency than in previous studies. Notably, gain at 20q13 was detected in almost all cases (97%), suggesting that this may play an important role in the pathogenesis of gastric cancer. By comparing the array CGH data with expression profiles of the same samples, we showed that both genomic amplification and deletion strongly influence the expression of genes in altered genomic regions. Furthermore, we identified 125 candidate genes, consisting of 114 up-regulated genes located in recurrent regions (>10%) of amplification and 11 down-regulated genes located in recurrent regions of deletion. Up-regulation of several candidate genes, such as CDC6, SEC61G, ANP32E, BYSL and FDFT1, was confirmed by immunohistochemistry. Interestingly, some candidate genes were localized at genomic loci adjacent to well-known genes such as EGFR, ERBB2 and SMAD4, and concordantly deregulated by genomic alterations. Based on these results, we propose that our list of candidate genes may contain novel genes involved in the pathogenesis of advanced gastric cancer. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.