Cross-platform array comparative genomic hybridization meta-analysis separates hematopoietic and mesenchymal from epithelial tumors

Cross-platform array comparative genomic hybridization meta-analysis separates hematopoietic and mesenchymal from epithelial tumors
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DOI:
10.1038/sj.onc.1209919
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发表时间:
2007-03-01
期刊:
影响因子:
8
通讯作者:
Ylstra, B.
Ylstra, B.
中科院分区:
医学1区
文献类型:
--
作者:
Jong, K.;Marchiori, E.;Ylstra, B.

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已经发表了一系列研究,使用阵列比较基因组杂交(阵列CGH)评价不同肿瘤类别的染色体拷贝数变化;然而,区分不同肿瘤类别的染色体畸变尚未得到充分表征。因此,我们对不同阵列CGH数据集进行了荟萃分析,试图对不同平台上检测的样本进行分类。与RNA表达相反,在双通道CGH阵列中使用了一种常见的参考:正常人DNA,理论上有利于跨平台分析。为此,整合了来自四个不同研究所的三个不同双通道阵列CGH平台的细胞系和原发性癌症数据集。细胞系数据用于开发预处理方法,该方法进行降噪并将样本转换为通用格式。转化后的阵列CGH图谱允许按细胞系进行完美聚类,但重要的是不允许按平台或研究所进行聚类。将用于细胞系数据的相同预处理程序应用于来自373个原发性肿瘤患者的数据。由阵列CGH引导,包括对照。结果表明,没有与研究所或平台相关的明显特征,并且阵列CGH允许进行明确的跨平台荟萃分析。鉴定了具有共同组织来源的主要簇。有趣的是,造血和间充质起源的肿瘤与上皮起源的肿瘤分开聚集。因此,可以得出结论,造血和间充质来源的肿瘤与上皮来源的肿瘤的染色体畸变是不同的,并且这些差异可以通过阵列CGH数据的荟萃分析来提取。这表明了前瞻性地使用不同拷贝数数据集的组合分析用于癌症亚型分类的可能性。
A series of studies have been published that evaluate the chromosomal copy number changes of different tumor classes using array comparative genomic hybridization ( array CGH); however, the chromosomal aberrations that distinguish the different tumor classes have not been fully characterized. Therefore, we performed a meta-analysis of different array CGH data sets in an attempt to classify samples tested across different platforms. As opposed to RNA expression, a common reference is used in dual channel CGH arrays: normal human DNA, theoretically facilitating cross-platform analysis. To this aim, cell line and primary cancer data sets from three different dual channel array CGH platforms obtained by four different institutes were integrated. The cell line data were used to develop preprocessing methods, which performed noise reduction and transformed samples into a common format. The transformed array CGH profiles allowed perfect clustering by cell line, but importantly not by platform or institute. The same preprocessing procedures used for the cell line data were applied to data from 373 primary tumors pro. led by array CGH, including controls. Results indicated that there is no apparent feature related to the institute or platform and that array CGH allows for unambiguous cross-platform meta-analysis. Major clusters with common tissue origin were identified. Interestingly, tumors of hematopoietic and mesenchymal origins cluster separately from tumors of epithelial origin. Therefore, it can be concluded that chromosomal aberrations of tumors from hematopoietic and mesenchymal origin versus tumors of epithelial origin are distinct, and these differences can be picked up by meta-analysis of array CGH data. This suggests the possibility of prospectively using combined analysis of diverse copy number data sets for cancer subtype classification.