Integrative Genome-Wide Analysis Reveals a Robust Genomic Glioblastoma Signature Associated with Copy Number Driving Changes in Gene Expression
Integrative Genome-Wide Analysis Reveals a Robust Genomic Glioblastoma Signature Associated with Copy Number Driving Changes in Gene Expression
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DOI：
10.1002/gcc.20618
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发表时间：
2009-01-01
影响因子：
3.7
通讯作者：
Mosser, Jean
中科院分区：
文献类型：
--
作者：
de Tayrac, Marie;Etcheverry, Arnandine;Mosser, Jean
多形性胶质母细胞瘤表现为多染色体畸变，其对基因表达的影响尚不清楚。为了研究这种关系并确定假定的启动基因组事件，我们使用全人类基因组阵列对胶质母细胞瘤的配对拷贝数和基因表达进行了调查。复发性拷贝数改变的位点与同一肿瘤样本上获得的基因表达谱相结合。我们确定了一组406个“顺式作用DNA靶向基因”，这些基因对应于基因表达的直接拷贝数驱动变化的基因组畸变，定义为DNA拷贝数和表达显著一致或相关变化的基因。功能注释揭示了这些基因参与癌细胞生物学的关键过程，为研究胶质母细胞瘤的遗传机制提供了新的思路。基因选择的稳健性在包括81个胶质母细胞瘤和23个非肿瘤性脑样本的外部微阵列数据集上得到验证。阵列CGH和基因表达数据的整合突出了一个强大的顺式作用DNA靶向基因特征，这可能对胶质母细胞瘤的进展至关重要，其中两个肿瘤抑制基因PCDH9和STARD13可能参与肿瘤侵袭和对依托波苷的抗性。(C) 2008 Wiley-Liss, Inc。
Glioblastoma multiforme shows multiple chromosomal aberrations, the impact of which on gene expression remains unclear. To investigate this relationship and to identify putative initiating genomic events, we integrated a paired copy number and gene expression survey in glioblastoma using whole human genome arrays. Loci of recurrent copy number alterations were combined with gene expression profiles obtained on the same tumor samples. We identified a set of 406 "cis-acting DNA targeted genes" corresponding to genomic aberrations with direct copy-number-driving changes in gene expression, defined as genes with either significantly concordant or correlated changes in DNA copy number and expression. Functional annotation revealed that these genes participate in key processes of cancer cell biology, providing insights into the genetic mechanisms driving glioblastoma. The robustness of the gene selection was validated on an external microarray data set including 81 glioblastomas and 23 non-neoplastic brain samples. The integration of array CGH and gene expression data highlights a robust cis-acting DNA targeted genes signature that may be critical for glioblastoma progression, with two tumor suppressor genes PCDH9 and STARD13 that could be involved in tumor invasiveness and resistance to etoposide. (C) 2008 Wiley-Liss, Inc.