Project description:Embryonal rhabdomyosarcoma (ERMS) is the most common soft tissue cancer in children and is characterized by myogenic differentiation arrest. The prognosis of patients with relapsed or metastatic disease remains poor. ERMS genomes show few recurrent mutations, suggesting that other molecular mechanisms such as epigenetic regulation might play major role in driving ERMS tumor biology. In this study, we have demonstrated the diverse roles of HDACs in the pathogenesis of ERMS by characterizing effects of HDAC inhibitors, trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; also known as vorinostat) in vitro and in vivo. TSA and SAHA suppress ERMS tumor growth and progression by inducing myogenic differentiation as well as reducing the self-renewal and migratory capacity of ERMS cells. To identify candidate genes that are differentially regulated in histone deacetylase inhibitor-treated embryonal rhabdomyosarcoma, a gene expression profiling study using the Affymetrix Human Gene 2.0 microarray platform and ingenuity pathway analysis of differentially expressed genes were performed on RD and 381T cells treated with trichostatin A or dimethyl sulfoxide (treatment vehicle).
Project description:Genomic and clinical analyses of major amplification events in alveolar rhabdomyosarcoma Affymetrix SNP 50K XbaI chips were used to anaylyze 57 alveolar rhabdomyosarcoma samples and selected cases were further analyzed using Affymetrix SNP 250K StyI chips
Project description:A series of conditional mouse models of embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma and spindle cell sarcoma were generated and validated for relavence to corresponding human cancers. Conditional mouse models of embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma and spindle cell sarcoma were created by activation or deletion of Pax3:Fkhr, p53, Ptch1 or Rb1 genes.
Project description:Histone deacetylase inhibitors are a class of drug which rapidly induce hyperacetylation of histone proteins. Here, we aimed to study the association between HDACi-induced histone acetylation and changes in gene expression. To study the early responses to HDACi treatment we treated cells with three different concentrations of two HDACi, sodium valproate (VPA) and suberoylanilide hydroxamic acid over a short timecourse.
Project description:Frozen skeletal muscle, tumor adjacent skeletal muscle, Endothelial Rhabdomyosarcoma (ERMS) and Alveolar Rhabdomyosarcoma (ARMS) samples were profiled on Illumina bead array. Total RNA from primary resected samples were profiled to allow comparison of 1) normal skeletal muscle tissue with RMS samples and 2) ARMS with ERMS tumors.
Project description:Histone deacetylase inhibitors are a class of drug which rapidly induce hyperacetylation of histone proteins. Here, we aimed to study the association between HDACi-induced histone acetylation and changes in gene expression. To study the early responses to HDACi treatment we treated cells with three different concentrations of two HDACi, sodium valproate (VPA) and suberoylanilide hydroxamic acid over a short timecourse. AH LCL cells were treated with 0.2mM, 1mM or 5mM valproic acid (VPA) or 0.5, 2.5 or 12.5µM suberoylanilide hydroxamic acid (SAHA). GM12878 cells were treated with 1mM VPA. Samples were collected at 0, 30, 60 and 120 minutes. All experiments were carried out in triplicate. One replicate of AH LCL, 0.2mM VPA, 30min and one replicate of AH LCL, 5mM VPA, 30min were eliminated as outliers