Project description:The 1q gain is related to poor survival, and to a profile of cell cycle deregulation in Ewing's Sarcoma (ES). Tumor samples with 1q gain overexpress the gene DTL. We have silenced DTL in three ES cell lines in order to compare the differential expression pattern produced with the differential expression pattern which characterizes 1q gained-tumors.
Project description:The 1q gain is related to poor survival, and to a profile of cell cycle deregulation in Ewing's Sarcoma (ES). Tumor samples with 1q gain overexpress the gene DTL. We have silenced DTL in three ES cell lines in order to compare the differential expression pattern produced with the differential expression pattern which characterizes 1q gained-tumors. We silenced DTL in three ES cell lines with two different shRNA constructions by means of lentiviral transduction. pLKO.1-non-targeting control was transduced in the control samples. RNA was extracted and hybridized with Affymetrix expression microarrays.
Project description:Amplification or gain of chromosome 1q (+1q) is a common genomic alteration occurring in nearly 40% of multiple myeloma patients. Although it is associated with poor prognosis and advanced disease stages, the impact of +1q at the proteomic level remains unclear. Here, we studied sorted CD138+ plasma cells from the bone marrow from newly diagnosed multiple myeloma to uncover molecular alterations associated with +1q. Differential expression analysis revealed significantly increased expression of several proteins encoded by 1q region indicating potential gene dosage effect. Protein pathway enrichment analysis identified enrichment of cell cycle pathway among proteins with increased expression in +1q. Further, protein-protein interaction network analysis showed enrichment of MYC transcriptional targets including increased expression of TIPRL (located on 1q23) in +1q cases. In agreement with these findings, increased TIPRL transcript expression was correlated with +1q across different primary driver genomic alterations in MM in the CoMMPass dataset. High TIPRL protein expression was further associated with poor prognosis in cases with hyperdiploidy. Overall, this study highlights the role of proteomics in understanding molecular events associated with chromosomal alterations in multiple myeloma and identifying potential targets for further functional analysis.
Project description:Background: Gain and/or amplification of chromosome 1q are frequently found in Multiple Myeloma (MM). The number of 1q copies correlates with a poor prognosis. The aim of this work is to study the impact on the clinical outcome and the trascriptomic changes induced by Gain1q (3 copies of 1q, 3X) and amplification 1q (Amp1q, ≥4 copies of 1q, 4X) in MM patients enrolled in the CoMMpass study (NCT145429). Methods: Fluorescence in situ hybridization (FISH) in CD138+ purified bone marrow plasma cells was centralized and performed at baseline. The cut-off level for Gain1q was 10% of nuclei with ≥3 copies of 1q (3X), while Amp1q was defined as ≥ 20% of nuclei with ≥4 copies of 1q (4X). Transcriptome data from patients were used to find differentially expressed genes (DEGs) in gain (3X) and amp1q (4X) patients.
Project description:This SuperSeries is composed of the following subset Series: GSE31185: The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes developmental defects in zebrafish embryos GSE31186: The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes Ewing's-type tumors in zebrafish Refer to individual Series
Project description:This SuperSeries is composed of the following subset Series: GSE20355: BAC-microarrays aCGH data from 67 Ewing's Sarcoma tumor samples and 16 Ewing's Sarcoma cell lines GSE20356: Evaluation of copy number alterations in the Ewing's Sarcoma cell line SKES1 with Affymetrix 500k SNP microarray GSE20357: Expression data from DTL silenced-Ewing Sarcoma's cell lines along with their controls Refer to individual Series
Project description:This SuperSeries is composed of the following subset Series: GSE37370: microRNA expression data from Ewing's sarcoma tumor samples GSE37371: Expression data from Ewing's sarcoma tumor samples Refer to individual Series
Project description:Genome wide DNA methylation profiling of Rhabdoid tumor of the kidney, Clear cell sarcoma of the kidney, Ewing's sarcoma family of tumors and non-neoplastic kidney. The Illumina Infinium HumanMethylation 27 BeadChip was used to obtain DNA methylation profiles across approximately 27000 CpGs . Samples included 3 Rhabdoid tumor of the kidney, 3 Clear cell sarcoma of the kidney, 3 Ewing's sarcoma family of tumor and 3 non-neoplastic kidney.
