Candidate glioblastoma development gene identification using concordance between copy number abnormalities and gene expression level changes
Candidate glioblastoma development gene identification using concordance between copy number abnormalities and gene expression level changes
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DOI：
10.1002/gcc.20474
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发表时间：
2007-10-01
影响因子：
3.7
通讯作者：
Cowell, John K.
中科院分区：
文献类型：
--
作者：
Lo, Ken C.;Rossi, Michael R.;Cowell, John K.
肿瘤细胞中的拷贝数异常（CNA）被认为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调查了30个胶质母细胞瘤中的丢失、获得和扩增，并将这些数据与使用Affytek U133Plus2.0寡核苷酸阵列的相同肿瘤中的基因表达变化进行了比较。这两个数据集使用我们的内部叠加工具进行叠加，该工具突出了相同肿瘤的CNA和表达水平变化之间的一致性。在这项调查中，我们强调了在1号，4号，11号和12号染色体上的扩增区域中经常过表达的基因，并在这些染色体上鉴定了新的扩增子。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基因表达的降低相关。此外，我们描述了一种新的方法，用于比较肿瘤之间的基因表达水平的基础上存在或不存在的染色体CNA。这种全基因组筛选提供了对可能作为GBM中CNA驱动因子的基因的有效和全面的调查。
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.