Project description:Ewingâs Sarcoma (ES) is characterized by specific chromosomal translocations, the most common being t(11;22)(q24;q12). Additionally, other types of genetic abnormalities may occur and be relevant to explain the variable tumoural biology and clinical outcome. We have carried out a high-resolution array CGH and expression profiling on 25 ES tumour samples to characterize the DNA copy number aberrations (CNA) occurring in these tumours and to determine their association with gene expression profiles (GEO Series accession number: GSE8303) and their clinical outcome. CNA were observed in 84% of the cases. We observed a median number of 3 aberrations per case. Besides numerical chromosomal changes, smaller aberrations were found and defined at chromosomes 5p, 7q and 9p. All CNA were compiled to define the smallest overlapping regions of imbalance (SORI). Thirty five SORI were delimited. Bioinformatic analyses were conducted to identify subgroups according to the pattern of genomic instability obtained. Unsupervised and supervised clustering analyses (using SORI as variables) segregated the tumours into two distinct groups: one genomically stable (⤠3 CNA) and another genomically unstable one (> 3 CNA). The genomic unstable group showed a statistically significant shorter overall survival and was more refractory to chemotherapy. This report elucidates data about genomic instability in ES, based on CNA and expression profiling for the first time, and shows that a genomically unstable group of Ewing tumours is correlated with a significant poor prognosis. Experiment Overall Design: Comparative experiment: pheripheral blood pool of ten healthy female donors: CONTROL vs. 26 Ewing Sarcoma Tumour Samples. Experiment Overall Design: Note that although 26 samples were profiled, only 25 were analysed (sample #11 did not pass quality control).
Project description:This SuperSeries is composed of the following subset Series: GSE30513: MicroRNA expression profiling of Ewing sarcoma cancer stem cells GSE31144: MicroRNA expression profiling of Ewing sarcoma cell lines upon TARBP2 depletion GSE31145: MicroRNA expression profiling of Ewing sarcoma spheres vs. adherent cells Refer to individual Series
Project description:We performed reduced representation bisulfite seqeuncing (RRBS) and ChIP-seq of histone modification marks on three Ewing sarcoma tumor samples, and we quantified epigenetic heterogeneity on three levels. First, we identified a Ewing sarcoma specific hypomethylation signature at EWS-FLI1 regulated enhancers, showing that epigenetic enhancer reprogramming is a defining feature of Ewing sarcoma. Second, inter-individual DNA methylation differences in Ewing sarcoma samples identified a continuous disease spectrum with two dimensions: the strength of the EWS-FLI1 regulatory signature and the balance of mesenchymal versus stem cell regulatory signatures. Third, we observed substantial epigenetic heterogeneity within individual tumors. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma, highlighting its importance as a source of variability for genetically homogeneous tumors.
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.