Transcriptional Heterogeneity of Progression in MYOD1-mutant spindle cell rhabdomyosarcoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE288065 | GEO | 2026/01/22
REPOSITORIES: GEO
Similar Datasets
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.
2011-02-17 | E-GEOD-22520 | biostudies-arrayexpress
Project description:Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both the pediatric and adult setting. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and adult-type pleomorphic rhabdomyosarcoma (PRMS) compared to embryonal rhabdomyosarcoma (ERMS). Recent genomic sequencing studies have expanded the spectrum of RMS, with several new molecularly defined entities, including fusion-driven spindle cell/sclerosing rhabdomyosarcoma (SC/SRMS) and MYOD1-mutant SC/SRMS. Comprehensive genomic analysis has previously defined the mutational and copy number spectrum for the more common ERMS and ARMS, as well as revealed corresponding methylation signatures. In contrast, genetic and epigenetic correlates have not been defined for the rare SC/SRMS or PRMS histologic subtypes. Herein, we present genomic sequencing, copy number analysis, and methylation profiling of the largest cohort of molecularly characterized RMS samples to date. We identified two novel methylation subtypes, one having SC/SRMS histology and defined by MYOD1 p. L122R mutations and the other matching adult type PRMS. Selected tumors from adolescent patients grouped with the PRMS methylation class, expanding the age range of these rare tumors. Pediatric patients in the MYOD1-mutant group, as well as those clustering with PRMS, appear to have poor overall survival.
2021-11-24 | GSE167059 | GEO
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.
2011-02-17 | GSE22520 | GEO
Project description:Genetic and shRNA-mediated inhibition of SIX1 expression in RMS cells induces myogenic differentiation and impedes RMS tumor growth. To elucidate the mechanism by which SIX1 loss activates a differentiation program, we performed SIX1, MYOD1, and H3K27ac ChIPseq in two SIX1 knockdown SMS-CTR cell lines and one control SMS-CTR cell line to profile changes in transcriptional activity and myogenic transcription factor binding in fusion-negative Rhabdomyosarcoma.
2022-02-07 | GSE173151 | GEO
Project description:Circular chromatin confirmation capture in rhabdomyosarcoma cells was performed with viewpoints at the PAX3-FOXO1 bound super enhancer upstream of MYOD1, and also at the MYOD1 promoter, to find support for looping between these two genetic elements almost 80 thousand base pairs apart.
2017-04-27 | GSE83727 | GEO
Project description:We generated the human ES lines, in which the genome-wide reduction of H3K27me3 can be induced by the ectopic expression of catalytic domain of histone demethylase JMJD3 with doxycycline treatment (JMJD3c-hESCs). The overexpression of JMJD3c enhances MYOD1-mediated myogenic differentiation of hESCs. We compared the gene expression patterns of the generated myogenic cells with those of human skeletal myotubes.
2016-10-18 | GSE80106 | GEO
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE126413 | GEO
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE126412 | GEO
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE126411 | GEO
Project description:Basic helix-loop-helix (bHLH) pioneer transcription factors Myod1 and Ascl1 are biochemically related but produce fundamentally different outcomes when expressed in fibroblasts: Myod1 produces muscle cells and Ascl1 induces neurons. Here, we sought to investigate the molecular mechanisms explaining the differential activity. Surprisingly, we found a large overlap in the overall binding patterns of Ascl1 and Myod1 in fibroblasts, with both transcription factors accessing both neuronal and myogenic targets. We also observed similar changes in chromatin accessibility and transcriptional activation. Yet, Myod1 predominantly induced a muscle program and Ascl1 a neuronal program. We found that differences in binding affinity at key targets resulted in largely distinct reprogramming outcomes. Accordingly, exchanging Myod1’s C-terminal protein-protein interacting domain and DNA-binding basic domain with those of Ascl1 induces an Ascl1-like binding and converts Myod1 into a pro-neuronal factor. Finally, we found that co-expression of Myod1 with the transcriptional repressor Myt1l inhibits induction of the muscle program and yields functional neuronal cells. Our findings are compatible with the notion that pioneer factor activity is associated with high-affinity protein-DNA and suggest that promiscuous binding of pioneer factors can induce unspecific lineage features which need to be kept in check by co-factor interactions.
2020-02-03 | GSE126410 | GEO