Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays
Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays
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DOI：
10.1038/sj.onc.1205868
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发表时间：
2002-10-03
期刊：
影响因子：
8
通讯作者：
Klein, B
中科院分区：
文献类型：
--
作者：
De Vos, J;Thykjær, T;Klein, B
DNA微阵列技术使得能够鉴定参与癌症中发生的细胞稳态的复杂失调的大量基因。我们使用Affyellow微阵列比较了9例多发性骨髓瘤（MM）患者和8个骨髓瘤细胞系的高度纯化恶性浆细胞与通过外周血B细胞体外分化获得的高度纯化非恶性浆细胞（8个样本）的基因表达谱。两种无监督聚类算法将这25个样本分为两个不同的聚类：恶性浆细胞聚类和正常浆细胞聚类。与正常血浆样本相比，恶性血浆样本中有250个基因显着上调，159个基因显着下调。对于这些基因中的一些，证实了编码蛋白的过表达或下调（细胞周期蛋白D1、c-myc、BMI-1、胱抑素c、cystatin、RB）。在骨髓瘤细胞中过度表达的两个基因（ABL和胱硫醚β合酶）编码的酶可能是特定药物的治疗靶点。这些数据为理解骨髓瘤疾病提供了新的见解，并预示着DNA微阵列的发展可能有助于开发癌症疾病的“点菜”治疗。
The DNA microarray technology enables the identification of the large number of genes involved in the complex deregulation of cell homeostasis taking place in cancer. Using Affymetrix microarrays, we have compared the gene expression profiles of highly purified malignant plasma cells from nine patients with multiple myeloma (MM) and eight myeloma cell lines to those of highly purified nonmalignant plasma cells (eight samples) obtained by in vitro differentiation of peripheral blood B cells. Two unsupervised clustering algorithms classified these 25 samples into two distinct clusters: a malignant plasma cell cluster and a normal plasma cell cluster. Two hundred and fifty genes were significantly up-regulated and 159 down-regulated in malignant plasma samples compared to normal plasma samples. For some of these genes, an overexpression or downregulation of the encoded protein was confirmed (cyclin D1, c-myc, BMI-1, cystatin c, SPARC, RB). Two genes over-expressed in myeloma cells (ABL and cystathionine beta synthase) code for enzymes that could be a therapeutic target with specific drugs. These data provide a new insight into the understanding of myeloma disease and prefigure that the development of DNA microarray could help to develop an 'a la carte' treatment in cancer disease.