Bandrés Eva, Malumbres Raquel, Escalada Alvaro, Cubedo Elena, González Iranzu, Honorato Beatriz, Zarate Ruth, García-Foncillas Jesus, de Alava Enrique
Laboratory of Pharmacogenomics, University of Navarra, Pamplona, Spain.
J Pediatr Hematol Oncol. 2005 Oct;27(10):537-42. doi: 10.1097/01.mph.0000184576.38835.e2.
The t(11;22)(q24;q12) translocation is present in up to 95% of Ewing tumor patients and results in the formation of an EWS-FLI-1 fusion gene that encodes a chimeric transcription factor. Many alternative forms of EWS-FLI-1 exist because of variations in the location of the EWS and FLI-1 genomic breakpoints. Previous reports have shown that the type 1 fusion is associated with a significantly better prognosis than the other fusion types. It has been suggested that the observed clinical discrepancies result from different transactivation potentials of the various EWS-FLI-1 fusion proteins. In an attempt to identify genes whose expression levels are differentially modulated by structurally different EWS-FLI-1 transcription factors, we have used microarray technology to interrogate 19,000 sequence genes to compare gene expression profile of type 1 or non-type 1 Ewing sarcoma cell lines. Data analysis showed few qualitative differences on gene expression; expression of only 41 genes (0.215% of possible sequences analyzed) differed significantly between Ewing tumor cell lines carrying EWS-FLI-1 fusion type 1 with respect to those with non-type 1 fusion.
高达95%的尤因肉瘤患者存在t(11;22)(q24;q12)易位，该易位导致EWS-FLI-1融合基因的形成，该基因编码一种嵌合转录因子。由于EWS和FLI-1基因组断点位置的差异，存在许多EWS-FLI-1的替代形式。先前的报告表明，1型融合与比其他融合类型显著更好的预后相关。有人提出，观察到的临床差异是由各种EWS-FLI-1融合蛋白不同的反式激活潜能导致的。为了鉴定那些表达水平受到结构不同的EWS-FLI-1转录因子差异调节的基因，我们使用微阵列技术检测了19000个序列基因，以比较1型或非1型尤因肉瘤细胞系的基因表达谱。数据分析显示基因表达上几乎没有定性差异；携带1型EWS-FLI-1融合的尤因肿瘤细胞系与携带非1型融合的细胞系相比，只有41个基因（占分析的可能序列的0.215%）的表达有显著差异。
