The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization.
The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization.
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DOI：
10.1186/1471-2407-12-235
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发表时间：
2012-06-12
期刊：
影响因子：
3.8
通讯作者：
Wang YC
中科院分区：
文献类型：
--
作者：
Lo FY;Chang JW;Chang IS;Chen YJ;Hsu HS;Huang SF;Tsai FY;Jiang SS;Kanteti R;Nandi S;Salgia R;Wang YC
癌症相关基因显示出种族差异。因此，鉴定和表征不同种族群体的DNA拷贝数改变区域有助于剖析肿瘤发生的机制。采用阵列-比较基因组杂交技术（array-CGH）分析了40例亚洲肺癌患者和20例高加索肺癌患者的DNA拷贝数谱。采用MetaCore分析疾病与通路相关性、array- cgh数据库与表达阵列数据库的一致性分析、拷贝数变异基因的文献检索等3种方法筛选新的肺癌候选基因。通过定量聚合酶链反应（qPCR）、显色原位杂交（CISH）、逆转录-qPCR （RT-qPCR）和免疫组织化学（IHC）对更多患者的4个候选癌基因进行了DNA拷贝数和mRNA及蛋白表达的验证。我们确定了20个包含459个基因的白种人染色体不平衡区域和17个包含476个基因的亚洲肺癌患者染色体不平衡区域。7个常见的染色体不平衡区包含117个基因，包括3p13-14、6p22.1、9q21.13、13q14.1和17p13.3；3p22 -22.3和13q13.3基因缺失在亚洲和高加索患者中均有发现。采用qPCR和RT-qPCR对Rho活性调控基因ARHGAP19 （10q24.1）、Wnt信号调控基因FRAT2 （10q24.1）、运动调控基因PAFAH1B1 （17p13.3）、MAPK信号调控基因ZNF322A （6p22.1）进行基因验证。4种候选基因在肿瘤组织中的平均基因剂量和mRNA表达量均显著高于相应的正常组织（P<0.001~P=0.06）。此外，对患者的CISH分析表明，肺癌患者中确实存在ARHGAP19和ZNF322A基因拷贝数扩增。亚洲白种人石蜡块的免疫组化分析表明，PAFAH1B1蛋白过表达的频率在亚洲人和白种人中分别为68%和70%。我们的研究提供了一个宝贵的数据库，揭示了亚洲和高加索肺癌患者在特定染色体上的共同和差异失衡区域。四种验证方法证实了我们的数据库，这将有助于进一步研究肺肿瘤发生的机制。
Cancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis. Array-comparative genomic hybridization (array-CGH) was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR), chromogenic in situ hybridization (CISH), reverse transcriptase-qPCR (RT-qPCR), and immunohistochemistry (IHC) in more patients. We identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1) functioning in Rho activity control, FRAT2 (10q24.1) involved in Wnt signaling, PAFAH1B1 (17p13.3) functioning in motility control, and ZNF322A (6p22.1) involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (P<0.001~P=0.06). In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of PAFAH1B1 protein overexpression was 68% in Asian and 70% in Caucasian. Our study provides an invaluable database revealing common and differential imbalance regions at specific chromosomes among Asian and Caucasian lung cancer patients. Four validation methods confirmed our database, which would help in further studies on the mechanism of lung tumorigenesis.
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影响因子：
11.2
作者：
Hou, Qingsong;Wu, Yong Hui;Tan, Patrick
通讯作者：
Tan, Patrick
DOI：
10.1006/bbrc.2001.4421
发表时间：
2001-03-02
影响因子：
3.1
作者：
Saitoh, T;Moriwaki, J;Katoh, M
通讯作者：
Katoh, M
影响因子：
6.4
作者：
Hayami, Shinya;Kelly, John D.;Hamamoto, Ryuji
通讯作者：
Hamamoto, Ryuji
影响因子：
8
作者：
Tseng, R-C;Lin, R-K;Wang, Y-C
通讯作者：
Wang, Y-C
影响因子：
2.6
作者：
Davies, JJ;Wilson, IM;Lam, WL
通讯作者：
Lam, WL