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胶质瘤标本采样及衍生细胞系中基因表达谱的稳健性

Robustness of gene expression profiling in glioma specimen samplings and derived cell lines.

作者信息

Mehrian Shai Ruty, Reichardt Juergen K V, Ya-Hsuan Hsu, Kremen Thomas J, Liau Linda M, Cloughesy Timothy F, Mischel Paul S, Nelson Stanley F

机构信息

Department of Human Genetics, UCLA Geffen School of Medicine, Los Angeles, CA 90095, USA.

出版信息

Brain Res Mol Brain Res. 2005 May 20;136(1-2):99-103. doi: 10.1016/j.molbrainres.2005.01.017.

Abstract

One of the most promising applications of microarrays is class distinction through gene expression profiling as a diagnostic tool. However, as there is apparent spatial heterogeneity in the morphology of cancer cells within a tumor, it is unclear if tumor sampling can be applied and yield consistent signals. In this report, we examined six brain tumors, four glioblastoma, and two oligodendroglioma biopsies. The six brain tumor tissues from two distinct different classes were dissected in four distinct areas and gene expression was profiled using microarrays. We used hierarchical clustering to compare the variability of gene expression profiles between spatially distinct biopsies of the same tumor as compared to the variability between tumors of the same histologic group. We conclude that, in general, repeat spatially distinct samples are not needed for microarray experiments and the gene expression signatures are robust across the tumor. Predominantly, variation was much greater between samples from different patients than from the multiple samplings of given tumor. Further, we compared biopsy expression profiles to the cell lines derived from those tissues. In general, the tumor cell lines vary greatly from the parental tissues and cluster more strongly with each other than the parental tissue. We select and examine the set of genes altered in expression to allow adaptation to cell culture.

摘要

微阵列最具前景的应用之一是通过基因表达谱进行类别区分,以此作为一种诊断工具。然而,由于肿瘤内癌细胞形态存在明显的空间异质性,尚不清楚肿瘤采样是否可行并能产生一致的信号。在本报告中,我们检查了六个脑肿瘤活检样本,其中四个是胶质母细胞瘤,两个是少突胶质细胞瘤。将来自两个不同类别的六个脑肿瘤组织在四个不同区域进行解剖,并使用微阵列对基因表达进行分析。我们使用层次聚类来比较同一肿瘤在空间上不同活检样本之间基因表达谱的变异性,与同一组织学组肿瘤之间的变异性。我们得出结论,一般来说,微阵列实验不需要重复进行空间上不同的样本检测,并且基因表达特征在整个肿瘤中是稳健的。主要地,不同患者样本之间的差异远大于给定肿瘤多次采样之间的差异。此外,我们将活检样本的表达谱与源自这些组织的细胞系进行了比较。一般来说,肿瘤细胞系与亲代组织差异很大,并且彼此之间的聚类比亲代组织更强。我们选择并检查了表达发生改变的基因集,以使其适应细胞培养。

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