Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA307509 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Translocation events are frequent in cancer and may create chimeric fusions or ‘regulatory rearrangements’ that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps reveal distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Remarkably, MYB protein binds to the translocated enhancers, creating a positive feedback loop that sustains its expression. MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. Bromodomain inhibitors slow tumor growth in ACC primagraft models in vivo. Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in the alternate ACC lineages.
2016-02-01 | GSE76465 | GEO
Project description:Translocations that drive overexpression of the oncogenic transcription factor MYB are molecular hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor. Surgical resection, whenever possible, is the standard therapy for ACC, but there are no available therapeutic options available if surgery fails. Here we performed a chemical genetic screen using a zebrafish embryo culture system and identified retinoic acid agonists as potent suppressors of c-myb. Retinoic acid treatment strongly decreased c-myb gene expression in U937 cells and suggested a direct transcriptional mechanism of regulation. Retinoic acid agonists strongly inhibited tumor growth in vivo in different ACC patient derived xenograft models. Analysis of the xenografts revealed a significant decrease in MYB binding at translocated enhancers, thereby disrupting the MYB positive feedback loop that drives ACC. Our findings identify an important role of retinoic acid in MYB regulation and as a potential new effective therapy for ACC.
2018-08-11 | GSE98007 | GEO
Project description:Translocations that drive overexpression of the oncogenic transcription factor MYB are molecular hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor. Surgical resection, whenever possible, is the standard therapy for ACC, but there are no available therapeutic options available if surgery fails. Here we performed a chemical genetic screen using a zebrafish embryo culture system and identified retinoic acid agonists as potent suppressors of c-myb. Retinoic acid treatment strongly decreased c-myb gene expression in U937 cells and suggested a direct transcriptional mechanism of regulation. Retinoic acid agonists strongly inhibited tumor growth in vivo in different ACC patient derived xenograft models. Analysis of the xenografts revealed a significant decrease in MYB binding at translocated enhancers, thereby disrupting the MYB positive feedback loop that drives ACC. Our findings identify an important role of retinoic acid in MYB regulation and as a potential new effective therapy for ACC.
2018-08-11 | GSE98006 | GEO
Project description:Translocation events are frequent in cancer and may create chimeric fusions or regulatory rearrangements that drive oncogene overexpression. Although regulatory rearrangements are increasingly recognized in hematopoietic and even solid tumors, the underlying mechanisms remain obscure. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a unifying theme in adenoid cystic carcinoma (ACC). Whole genome sequencing data and chromatin state maps for 13 primary tumors and xenografts reveal distinct chromosomal rearrangements that juxtapose super-enhancer clusters to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers physically interact with the MYB promoter. Remarkably, the MYB product itself binds to the translocated enhancers, thus creating a positive feedback loop that sustains its own expression. MYB also binds a large number of active enhancers that drive opposing regulatory programs in alternate cell lineages in ACC. MYB cooperates with the transcription factor TP63 in the myoepithelial component of the tumors, but promotes a Notch program in the luminal epithelial component. Bromodomain inhibitors, which disrupt enhancer function, slow tumor growth in ACC primagraft models in vivo, but are ineffective against high grade tumors that harbor activating mutations in the Notch pathway. Thus, our study identifies super-enhancer translocations as a unifying feature of ACC, and provides insight into the mechanism by which sustained MYB overexpression drives alternate cell fates in this disease.
Processed ChIP-seq data is available on GEO under accession number GSE76465.
| EGAS00001001457 | EGA
Project description:Chromatin immunoprecipitation was carried out using an anti-MYB antibody in PDX-derived ACCX11 adenoid cystic carcinoma cells. Input samples were extracted prior to the addition of antibody.
2023-12-01 | E-MTAB-12976 | biostudies-arrayexpress
Project description:Retinoic acid suppresses MYB in adenoid cystic carcinoma
| PRJNA383650 | ENA
Project description:tracheal adenoid cystic carcinoma is one kind of non-small-cell lung cancer with limit treatment options. We used single cell RNA sequencing (scRNA-seq) to analyze the molecular characteristic of tracheal adenoid cystic carcinoma, aiming to recognized this disease deeply and provide potential treatment plan in the future.
2024-10-31 | GSE245170 | GEO
Project description:Retinoic acid suppresses MYB in adenoid cystic carcinoma [RNA-seq]
| PRJNA383655 | ENA
Project description:Retinoic acid suppresses MYB in adenoid cystic carcinoma [ChIP-seq]
| PRJNA383656 | ENA
Project description:The MYB-NFIB gene is a driver-mutation in the majority of adenoid cystic carcinomas (ACCs) and believed to control a large number of genes involved in tumorigenesis. This experiment investigates the effects on gene expression after siRNA knock-down of MYB-NFIB and/or inhibition of IGF1R/INSR signaling in ACC cells.
2018-06-01 | GSE76094 | GEO