Changes in WT1 splicing are associated with a specific gene expression profile in Wilms' tumour
Changes in WT1 splicing are associated with a specific gene expression profile in Wilms' tumour
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DOI：
10.1038/sj.onc.1205752
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发表时间：
2002-08-15
期刊：
影响因子：
8
通讯作者：
Jeanpierre, C
中科院分区：
文献类型：
--
作者：
Baudry, D;Faussillon, M;Jeanpierre, C
肾母细胞瘤 (WT) 或肾母细胞瘤是儿童中最常见的肾癌。在之前的一项研究中，我们报告了 90% 的 WT 测试中 WTI 转录发生改变，其中外显子 5 +/- 同工型比率降低是最常见的改变（WT 的 56%）。我们现在报告了一种基于肿瘤池 cDNA 分析的方法，以识别可能与 WTI 外显子 5 +/- 比率降低相关的失调基因。我们使用 Atlas Cancer cDNA 表达阵列比较了根据是否存在这种异构体不平衡（五个肿瘤）或不存在（四个肿瘤）分类的肿瘤库的表达谱。测试的 588 个基因中有 14 个在外显子 5 +/- 比率降低的肿瘤池中显示出特异性上调（CCND2、PCNA、N-MYC、E2F3、TOP2A、PAK1、DCC 和 PCDH2）或下调（VEGF、IGFBP5、TIMP3、ARHB、C-FOS 和 CD9）。这些结果通过四个基因（CCND2、PCNA、VEGF 和 IGFBP5）的 RT-PCR 分析得到验证。我们通过实时 RTPCR 将 VEGF 表达分析扩展到 51 个肿瘤，并确定了该基因与 WTI 表达模式相关的差异表达。此外，我们的结果表明 VEGF 表达水平可能与复发患者的预后相关。
Wilms' tumour (WT) or nephroblastoma is the most frequent kidney cancer in children. In a previous study, we reported alterations to WTI transcription in 90% of WT tested, with decreased exon 5 +/- isoform ratio being the most frequent alteration (56% of WT). We now report an approach based on cDNA profiling of tumour pools to identify genes likely to be dysregulated in association with a decreased WTI exon 5 +/- ratio. We compared the expression profiles of pools of tumours classified according to whether this isoform imbalance was present (five tumours) or not (four tumours), using Atlas Cancer cDNA expression arrays. Fourteen of 588 genes tested displayed specific up-regulation (CCND2, PCNA, N-MYC, E2F3, TOP2A, PAK1, DCC and PCDH2) or down-regulation (VEGF, IGFBP5, TIMP3, ARHB, C-FOS and CD9) in the pool of tumours with decreased exon 5 +/- ratio. These results were validated by RT-PCR analysis of four genes (CCND2, PCNA, VEGF and IGFBP5). We extended the analysis of VEGF expression to 51 tumours by real-time RTPCR and ascertained differential expression of this gene associated with WTI expression pattern. Moreover, our results suggest that the VEGF expression level may be of prognosis relevance for relapsed patients.