Lo Ken C, Rossi Michael R, LaDuca Jeffrey, Hicks David G, Turpaz Yaron, Hawthorn Lesleyann, Cowell John K
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Genes Chromosomes Cancer. 2007 Oct;46(10):875-94. doi: 10.1002/gcc.20474.
Copy number abnormalities (CNAs) in tumor cells are presumed to affect expression levels of genes located in region of abnormality. To investigate this relationship we have surveyed the losses, gains and amplifications in 30 glioblastomas using array comparative genome hybridization and compared these data with gene expression changes in the same tumors using the Affymetrix U133Plus2.0 oligonucleotide arrays. The two datasets were overlaid using our in-house overlay tool which highlights concordance between CNAs and expression level changes for the same tumors. In this survey we have highlighted genes frequently overexpressed in amplified regions on chromosomes 1, 4, 11, and 12 and have identified novel amplicons on these chromosomes. Deletions of specific regions on chromosomes 9, 10, 11, 14, and 15 have also been correlated with reduced gene expression in the regions of minimal overlap. In addition we describe a novel approach for comparing gene expression levels between tumors based on the presence or absence of chromosome CNAs. This genome wide screen provides an efficient and comprehensive survey of genes which potentially serve as the drivers for the CNAs in GBM.
肿瘤细胞中的拷贝数异常（CNA）被认为会影响位于异常区域的基因的表达水平。为了研究这种关系，我们使用阵列比较基因组杂交技术检测了30例胶质母细胞瘤中的缺失、增加和扩增情况，并使用Affymetrix U133Plus2.0寡核苷酸阵列将这些数据与同一肿瘤中的基因表达变化进行了比较。使用我们内部的叠加工具将这两个数据集进行叠加，该工具突出显示了同一肿瘤中CNA与表达水平变化之间的一致性。在这项研究中，我们强调了在染色体1、4、11和12的扩增区域中经常过度表达的基因，并在这些染色体上鉴定出了新的扩增子。染色体9、10、11、14和15上特定区域的缺失也与最小重叠区域中的基因表达降低相关。此外，我们描述了一种基于染色体CNA的存在与否来比较肿瘤之间基因表达水平的新方法。这种全基因组筛选为可能作为胶质母细胞瘤中CNA驱动因素的基因提供了高效且全面的研究。
