PAX translocations remodel mitochondrial metabolism through altered leucine usage in rhabdomyosarcoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1067626 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27682002_1.fastq.gz | Fastqsanger.gz | |||
| SRR27682002_2.fastq.gz | Fastqsanger.gz | |||
| SRR27682003_1.fastq.gz | Fastqsanger.gz | |||
| SRR27682003_2.fastq.gz | Fastqsanger.gz | |||
| SRR27682004_1.fastq.gz | Fastqsanger.gz |
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Project description:PAX translocations remodel mitochondrial metabolism through altered leucine usage in rhabdomyosarcoma [pcHiC_HiC]
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Project description:PAX translocations remodel mitochondrial metabolism through altered leucine usage in rhabdomyosarcoma [Cut&Run]
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Project description:PAX translocations remodel mitochondrial metabolism through altered leucine usage in rhabdomyosarcoma [RNA-seq]
| PRJNA1067627 | ENA
Project description:Alveolar rhabdomyosarcoma (ARMS) patients harboring PAX3-FOXO1 and PAX7-FOXO1 fusion proteins exhibit a greater incidence of tumor relapse, metastasis, and poor survival outcome, thereby underscoring the urgent need to develop effective therapies to treat this subtype of childhood cancer. To uncover mechanisms that contribute to tumor initiation, we develop a muscle progenitor model and use epigenomic approaches to unravel genome rewiring events mediated by PAX3/7 fusion proteins. Among the key targets of PAX3/7 fusion proteins, we identify a cohort of oncogenes, FGF receptors, tRNA-modifying enzymes, and genes essential for mitochondrial metabolism and protein translation, which we successfully targeted in preclinical trials. We identify leucine usage as a key factor driving the growth of aggressive PAX-fusion tumors, as limiting its bioavailability impaired oxidative phosphorylation and mitochondrial metabolism, delaying tumor progression and improving survival in vivo. Our data provide a compelling list of actionable targets and suggest promising new strategies to treat this tumor. This SuperSeries is composed of the SubSeries listed below.
2025-04-03 | GSE253895 | GEO
Project description:Alveolar rhabdomyosarcoma (ARMS) patients harboring PAX3-FOXO1 and PAX7-FOXO1 fusion proteins exhibit a greater incidence of tumor relapse, metastasis, and poor survival outcome, thereby underscoring the urgent need to develop effective therapies to treat this subtype of childhood cancer. To uncover mechanisms that contribute to tumor initiation, we develop a muscle progenitor model and use epigenomic approaches to unravel genome rewiring events mediated by PAX3/7 fusion proteins. Among the key targets of PAX3/7 fusion proteins, we identify a cohort of oncogenes, FGF receptors, tRNA-modifying enzymes, and genes essential for mitochondrial metabolism and protein translation, which we successfully targeted in preclinical trials. We identify leucine usage as a key factor driving the growth of aggressive PAX-fusion tumors, as limiting its bioavailability impaired oxidative phosphorylation and mitochondrial metabolism, delaying tumor progression and improving survival in vivo. Our data provide a compelling list of actionable targets and suggest promising new strategies to treat this tumor.
2025-04-03 | GSE253894 | GEO
Project description:Alveolar rhabdomyosarcoma (ARMS) patients harboring PAX3-FOXO1 and PAX7-FOXO1 fusion proteins exhibit a greater incidence of tumor relapse, metastasis, and poor survival outcome, thereby underscoring the urgent need to develop effective therapies to treat this subtype of childhood cancer. To uncover mechanisms that contribute to tumor initiation, we develop a muscle progenitor model and use epigenomic approaches to unravel genome rewiring events mediated by PAX3/7 fusion proteins. Among the key targets of PAX3/7 fusion proteins, we identify a cohort of oncogenes, FGF receptors, tRNA-modifying enzymes, and genes essential for mitochondrial metabolism and protein translation, which we successfully targeted in preclinical trials. We identify leucine usage as a key factor driving the growth of aggressive PAX-fusion tumors, as limiting its bioavailability impaired oxidative phosphorylation and mitochondrial metabolism, delaying tumor progression and improving survival in vivo. Our data provide a compelling list of actionable targets and suggest promising new strategies to treat this tumor.
2025-04-03 | GSE253893 | GEO
Project description:Alveolar rhabdomyosarcoma (ARMS) patients harboring PAX3-FOXO1 and PAX7-FOXO1 fusion proteins exhibit a greater incidence of tumor relapse, metastasis, and poor survival outcome, thereby underscoring the urgent need to develop effective therapies to treat this subtype of childhood cancer. To uncover mechanisms that contribute to tumor initiation, we develop a muscle progenitor model and use epigenomic approaches to unravel genome rewiring events mediated by PAX3/7 fusion proteins. Among the key targets of PAX3/7 fusion proteins, we identify a cohort of oncogenes, FGF receptors, tRNA-modifying enzymes, and genes essential for mitochondrial metabolism and protein translation, which we successfully targeted in preclinical trials. We identify leucine usage as a key factor driving the growth of aggressive PAX-fusion tumors, as limiting its bioavailability impaired oxidative phosphorylation and mitochondrial metabolism, delaying tumor progression and improving survival in vivo. Our data provide a compelling list of actionable targets and suggest promising new strategies to treat this tumor.
2025-04-03 | GSE253892 | GEO
Project description:Alveolar rhabdomyosarcomas (ARMS) are aggressive soft-tissue sarcomas affecting children and young adults. Most ARMS tumors express the PAX3-FKHR or PAX7-FKHR (PAX-FKHR) fusion genes resulting from the t(2;13) or t(1;13) chromosomal translocations, respectively. However, up to 25% of ARMS tumors are fusion negative, making it unclear whether ARMS represent a single disease or multiple clinical and biological entities with a common phenotype. To test to what extent PAX-FKHR determine class and behavior of ARMS, we used oligonucleotide microarray expression profiling on 139 primary rhabdomyosarcoma tumors and an in vitro model. We found that ARMS tumors expressing either PAX-FKHR gene share a common expression profile distinct from fusion-negative ARMS and from the other rhabdomyosarcoma variants. We also observed that PAX-FKHR expression above a minimum level is necessary for the detection of this expression profile. Using an ectopic PAX3-FKHR and PAX7-FKHR expression model, we identified an expression signature regulated by PAX-FKHR that is specific to PAX-FKHR-positive ARMS tumors. Data mining for functional annotations of signature genes suggested a role for PAX-FKHR in regulating ARMS proliferation and differentiation. Cox regression modeling identified a subset of genes within the PAX-FKHR expression signature that segregated ARMS patients into three risk groups with 5-year overall survival estimates of 7%, 48%, and 93%. These prognostic classes were independent of conventional clinical risk factors. Our results show that PAX-FKHR dictate a specific expression signature that helps define the molecular phenotype of PAX-FKHR-positive ARMS tumors and, because it is linked with disease outcome in ARMS patients, determine tumor behavior. NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897589792480:1'
2016-12-22 | GSE92689 | GEO
Project description:modENCODE_submission_3856 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP117(official name : OP117 genotype : unc119(ed3);wgIs117(pax-1::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The PAX-1::EGFP fusion protein is expressed in the correct pax-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the PAX-1 transcription factor. made_by : Unknown ); Developmental Stage: embryo; Genotype: unc119(ed3);wgIs117(pax-1::TY1 EGFP FLAG;unc119); Sex: mixed Male and Hermaphrodite population; EXPERIMENTAL FACTORS: Developmental Stage embryo; Target gene pax-1; Strain OP117(official name : OP117 genotype : unc119(ed3);wgIs117(pax-1::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The PAX-1::EGFP fusion protein is expressed in the correct pax-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the PAX-1 transcription factor. made_by : Unknown ); temp (temperature) 20 degree celsius
2013-07-11 | E-GEOD-48722 | biostudies-arrayexpress
Project description:The use of peripheral blood mononuclear cells (PBMC) for transcriptome analysis has already been proven valuable for assessing disease-associated and drug response related gene signatures. While these proof-of-principle studies have been critically important, the instability of RNA within PBMC prohibits their use in large scale multi-center trials for which samples have to be transported for a prolonged time prior RNA isolation. Therefore, a prerequisite for transcriptome analysis of peripheral blood in clinical trials will be a standardized and valid method to immediately stabilize the RNA profile after blood withdrawal. We demonstrate that the globin mRNA reduction method results in significantly improved data quality of stabilized RNA samples resulting in low intra-group variance and a detection rate of expressed genes similar to PBMC. More important, even small differences in gene expression such as observed between females and males were detected and sufficient to predict gender in whole blood samples. Experiment Overall Design: Whole blood was drawn from 7 female and 7 male subjects into PAXgeneTM blood collection tubes. After isolation of total RNA, a subset of each RNA sample was subjected to a globin reduction protocol (GRP) Microarray analysis was performed from PAX and GRP samples using Affymetrix U133A arrays. Experiment Overall Design: Gene expression profiles of females and males were compared in the PAX and the GRP group.
2008-06-12 | E-GEOD-2888 | biostudies-arrayexpress