Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression
Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression
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DOI：
10.1073/pnas.161272798
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发表时间：
2001-07-31
影响因子：
11.1
通讯作者：
Shipley, J
中科院分区：
文献类型：
--
作者：
Lu, YJ;Williamson, D;Shipley, J
基因表达的改变可在癌症发展和治疗、发育异常和分化过程中产生表型后果。在这里，我们描述了一种快速的方法，称为比较表达序列杂交（CESH），它给出了一个全基因组的观点，根据染色体位置的组织内的相对表达模式。不需要基因或克隆的先验知识，并且可以使用最少量的组织。表达谱以类似于通过比较基因组杂交分析鉴定染色体不平衡的方式获得。该方法被证明是指示染色体区域，该区域含有可能与耐药表型相关的过表达基因。此外，已知的和新的区域的差异基因表达在正常组织和肿瘤样本的软组织肉瘤组横纹肌肉瘤（RMS）的指示。这些区域包括2 p24; MYCN在2 p24的过表达通过定量逆转录PCR证实了所有肺泡RMS病例，并且不一定对应于基因组扩增。包括区域特异性微阵列分析在内的证据表明，CESH检测可能需要来自一个区域的几个基因的过表达。这一证据与影响特定基因组位置上许多基因表达的功能相关基因簇和机制一致。不同亚型RMS中表现出的独特CESH谱显示了肿瘤分类的潜力。
Altered expression of genes can have phenotypic consequences in cancer development and treatment, developmental abnormalities, and differentiation processes. Here we describe a rapid approach, termed comparative expressed sequence hybridization (CESH), which gives a genome-wide view of relative expression patterns within tissues according to chromosomal location. No prior knowledge of genes or cloning is required, and minimal amounts of tissue can be used. Expression profiles are achieved in a manner similar to the identification of chromosomal imbalances by comparative genomic hybridization analysis. The approach is demonstrated to indicate a chromosomal region that harbors overexpressed genes that may be associated with a drug-resistant phenotype. In addition, known and new regions of differential gene expression in both normal tissues and tumor samples from the soft tissue sarcoma group of rhabdomyosarcoma (RMS) are indicated. These regions included 2p24; overexpression of MYCN at 2p24 was confirmed by quantitative reverse transcription-PCR for all of the alveolar RMS cases and did not necessarily correspond to genomic amplification. Evidence including region specific microarray analysis indicated that overexpression of several genes from a region may be required for detection by CESH. This evidence is consistent with clusters of functionally related genes and mechanisms that affect the expression of a number of genes at a particular genomic location. The distinctive CESH profiles demonstrated in different subtypes of RMS show potential for tumor classification.