Gene Expression Profile of Ewing Sarcoma Cell Lines Differing in Their EWS-FLI1 Fusion Type

Abstract

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.

Growth-Promoting Role of the miR-106a∼363 Cluster in Ewing Sarcoma

“…[45] In microarray expression profiling of type 1 fusion compared to non-type 1 fusion bearing cells revealed 41 genes were differentially expressed, with all being downregulated in the non-type 1 fusion bearing cell lines. [47] These genes included genes involved in muscle development, proliferation, and calcium-ion binding, among others. However, the functional consequences of these differences have not been studied in detail.…”

Array CGH and gene-expression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing's sarcoma

“…Previous works have focused their research on array expression profiles of ES cell lines and primary tumours in order to identify tumour classification profiles, new EWS/FLI1 targets or to reveal distinct expression signatures associated to different outcomes (Khan et al, 2001;Ohali et al, 2004;Bandres et al, 2005;Mendiola et al, 2006). A more recent genomic approach is the use of array-based comparative genomic hybridization (aCGH), which has been successfully used for the detection of genomic imbalances in human tumours (Pinkel and Albertson, 2005) in a most precise manner than chromosome-based conventional techniques.…”

Genetics and Epigenetics of the TET-ETS Translocation Network

“…100 On the other hand, the consequences of TET-ETS fusion protein activity depend on the cellular background 101,102 and fusion type dependent differences in the gene expression profile of EFT have been observed. 103,104 The fusion type as well as the genes expression profile have been identified as prognostic factors for EFT patients. [105][106][107][108][109] The exact function of TET-ETS fusion proteins in cancer pathogenesis remains unclear.…”