Project description:Affymetrix exon array data were generated from total RNA that was isolated from localized Ewing sarcoma biopsy specimens. Expression of transcript summarized data was compared to data generated from normal stem cells and normal adult tissues. Total RNA was extracted from 32 archived tumor biopsy specimens obtained from patients with localized Ewing sarcoma. Samples were analyzed by Affymetrix exon arrays using standard procedures. Data were compared to human neural crest and mesenchymal stem cells (in triplicate: GSE21511) as well as to 33 normal adult tissues (Affymetrix tissue controls; 11 tissues in triplicate: cel files obtained from: http://www.affymetrix.com/support/technical/sample_data/exon_array_data.affx). Normalization was achieved by RMA using Parkek Genomics Suite
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:Affymetrix exon array data were generated from total RNA that was isolated from localized Ewing sarcoma biopsy specimens. Expression of transcript summarized data was compared to data generated from normal stem cells and normal adult tissues.
Project description:Epigenetic modifications have been shown to be important in developmental tumors as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors and 7 cell lines using the Infinium Human Methylation 450k. Differential methylation analysis between Ewing sarcoma and reference samples revealed 1,166 hypermethylated and 864 hypomethylated CpG sites (Bonferroni p<0.05, δ-β-value with absolute difference of >0.20) corresponding to 392 and 470 genes respectively. Gene Ontology analysis of genes differentially methylated in Ewing sarcoma samples showed a significant enrichment of developmental genes. Membrane and cell signal genes were also enriched, among those, 11 were related to caveola formation. We identified differential hypermethylation of CpGs located in the body and S-Shore of the PTRF gene in Ewing sarcoma that correlated with its repressed transcriptional state. Reintroduction of PTRF/Cavin-1 in Ewing sarcoma cells revealed a role of this protein as a tumor suppressor. Restoration of caveolae in the membrane of Ewing sarcoma cells, by exogenously reintroducing PTRF, disrupts the MDM2/p53 complex, which consequently results in the activation of p53 and the induction of apoptosis.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.