Identification of genes with a correlation between copy number and expression in gastric cancer.

Identification of genes with a correlation between copy number and expression in gastric cancer.
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DOI:
10.1186/1755-8794-5-14
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发表时间:
2012-05-04
影响因子:
2.7
通讯作者:
Zhang Q
Zhang Q
中科院分区:
医学3区
文献类型:
--
作者:
Cheng L;Wang P;Yang S;Yang Y;Zhang Q;Zhang W;Xiao H;Gao H;Zhang Q

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为了阐明与拷贝数变化相关的基因表达,我们对25对胃组织进行了全基因组拷贝数和表达微阵列分析。我们使用激光捕获显微解剖(LCM)获取样品进行微阵列实验,并使用244K CGH微阵列和Human Exon 1.0 ST微阵列分析DNA拷贝数和基因表达。显然,在最高频率(70%)检测到8q增益,在第二频率(63%)检测到20q增益。我们还确定了不同tnm分期或胃癌组织学亚型的分子遗传差异。有趣的是,C20orf11在20q13.33位点的扩增和增加几乎可以将中度分化(MD)型胃癌与低分化(PD)型胃癌区分开来。在无监督的双向分层聚类中,选择163个基因,显示基因拷贝数和表达之间的相关性,并鉴定出的基因能够区分匹配的邻近非癌样本和胃癌样本。对163个基因中的4个基因(C20orf11、XPO5、PUF60和PLOD3)进行定量RT-PCR分析,验证了芯片结果。值得注意的是,一些候选基因(MCM4和YWHAZ)及其邻近基因(PRKDC、UBE2V2、ANKRD46、ZNF706和GRHL2)都因基因组畸变而一致失调。综上所述,我们的研究结果揭示了不同tnm分期或不同组织学亚型胃癌的不同染色体区域改变,这有助于研究临床病理分类,并突出了一些有趣的基因作为胃癌的潜在生物标志物。
To elucidate gene expression associated with copy number changes, we performed a genome-wide copy number and expression microarray analysis of 25 pairs of gastric tissues. We applied laser capture microdissection (LCM) to obtain samples for microarray experiments and profiled DNA copy number and gene expression using 244K CGH Microarray and Human Exon 1.0 ST Microarray. Obviously, gain at 8q was detected at the highest frequency (70%) and 20q at the second (63%). We also identified molecular genetic divergences for different TNM-stages or histological subtypes of gastric cancers. Interestingly, the C20orf11 amplification and gain at 20q13.33 almost separated moderately differentiated (MD) gastric cancers from poorly differentiated (PD) type. A set of 163 genes showing the correlations between gene copy number and expression was selected and the identified genes were able to discriminate matched adjacent noncancerous samples from gastric cancer samples in an unsupervised two-way hierarchical clustering. Quantitative RT-PCR analysis for 4 genes (C20orf11, XPO5, PUF60, and PLOD3) of the 163 genes validated the microarray results. Notably, some candidate genes (MCM4 and YWHAZ) and its adjacent genes such as PRKDC, UBE2V2, ANKRD46, ZNF706, and GRHL2, were concordantly deregulated by genomic aberrations. Taken together, our results reveal diverse chromosomal region alterations for different TNM-stages or histological subtypes of gastric cancers, which is helpful in researching clinicopathological classification, and highlight several interesting genes as potential biomarkers for gastric cancer.
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