Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis
Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis
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DOI：
10.1182/blood-2003-01-0016
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发表时间：
2003-12-15
期刊：
影响因子：
20.3
通讯作者：
Anderson, KC
中科院分区：
文献类型：
--
作者：
Davies, FE;Dring, AM;Anderson, KC
为了确定正常浆细胞（PCs）向不确定意义单克隆γ病（MGUS）和多发性骨髓瘤（MM）多步骤转化过程中重要的特定途径，我们对5名健康供体(N)、7名MGUS患者和24名新诊断的MM患者的PCs进行了微阵列分析。使用125个基因进行无监督分层聚类，在所有样本中具有较大差异，定义了2组：N和MGUS/MM。经监督分析，共鉴定出263个N与MGUS差异表达基因和380个N与MM差异表达基因，其中197个基因在N与MGUS之间也存在差异表达。MGUS与MM样品之间只有74个基因存在差异表达，说明MGUS与MM样品之间的差异小于N与MM或N与MGUS样品之间的差异。差异表达的基因包括癌基因/肿瘤抑制基因（LAF4、RB1和失活同源基因2）、细胞信号传导基因（RAS家族成员、b细胞信号传导和NF-kappaB基因）、dna结合和转录因子基因（XBP1、锌指蛋白、叉头盒蛋白和无名指蛋白）以及发育基因（WNT和SHH通路）。通过基因表达谱分析了解MM的分子发病机制，揭示了从N到恶性pc的序列遗传变化，并强调了MGUS向MM转化的重要途径。
To define specific pathways important in the multistep transformation process of normal plasma cells (PCs) to monoclonal gammopathy of uncertain significance (MGUS) and multiple myeloma (MM), we have applied microarray analysis to PCs from 5 healthy donors (N), 7 patients with MGUS, and 24 patients with newly diagnosed MM. Unsupervised hierarchical clustering using 125 genes with a large variation across all samples defined 2 groups: N and MGUS/MM. Supervised analysis identified 263 genes differentially expressed between N and MGUS and 380 genes differentially expressed between N and MM, 197 of which were also differentially regulated between N and MGUS. Only 74 genes were differentially expressed between MGUS and MM samples, indicating that the differences between MGUS and MM are smaller than those between N and MM or N and MGUS. Differentially expressed genes included oncogenes/tumor-suppressor genes (LAF4, RB1, and disabled homolog 2), cell-signaling genes (RAS family members, B-cell signaling and NF-kappaB genes), DNA-binding and transcription-factor genes (XBP1, zinc finger proteins, forkhead box, and ring finger proteins), and developmental genes (WNT and SHH pathways). Understanding the molecular pathogenesis of MM by gene expression profiling has demonstrated sequential genetic changes from N to malignant PCs and highlighted important pathways involved in the transformation of MGUS to MM.