ChIP-seq of MYB in adenoid cystic carcinoma (ACC) ACCX11 cells
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ABSTRACT:
PROVIDER: PRJEB62574 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR11475477_1.fastq.gz | Fastqsanger.gz | |||
| ERR11475477_2.fastq.gz | Fastqsanger.gz | |||
| ERR11475478_1.fastq.gz | Fastqsanger.gz | |||
| ERR11475478_2.fastq.gz | Fastqsanger.gz | |||
| ERR11475479_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
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: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. 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:Adenoid cystic carcinoma (ACC) is one of the most common malignancies that arise in the salivary glands, with an incidence of 4.5 per 1,000,000. It can also arise in glandular tissue closely related to salivary glands in the lacrimal gland, nasal passages and tracheobronchial tree, as well as in glands of the breast and vulva. At all of these sites, it is characterized by a distinctive histology of basaloid epithelial cells arranged in cribriform or tubular patterns, usually demonstrating abundant hyaline extracellular matrix secretion and some degree of myoepithelial differentiation. ACC is generally a slow-growing tumor characterized by a protracted clinical course, usually well over 5 years in duration, marked by regional recurrence, distant metastasis and/or spread along peripheral nerves. A recurrent chromosomal translocation, t(6;9)(q23;p21), has been identified in ACC, and recently it has been discovered that in a majority of ACC the MYB gene on chromosome 6 is fused to the 3’ terminus of the NFIB gene on chromosome 9, creating a fusion gene product resulting in increased MYB-related transcriptional activation. Recently it has been determined that most cell lines with attribution of ACC derivation are either contaminants of other cell lines or do not have the characteristic MYB-NFIB translocation. Also, there are no animal models of this histologically and genetically defined tumor type. To address the paucity of experimental and pre-clinical models systems of ACC, we have for several years been establishing xenograft tumor lines from clinical samples of ACC. We describe our experience with these models and their characterization here. Analysis of 12 xenografts of human adenoid cystic carcinoma (ACC) along with 10 samples of ACC directly from humans. Note, that 12 of these samples are paired primary ACC & xenograft ACC from the same individual (6 pairs in total).
2011-05-03 | E-GEOD-28996 | biostudies-arrayexpress
Project description:Retinoic acid suppresses MYB in adenoid cystic carcinoma
| PRJNA383650 | ENA
Project description:MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
2015-03-13 | GSE59702 | GEO
Project description:MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
2015-03-13 | GSE59701 | GEO
Project description:MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
2015-03-13 | GSE59700 | GEO
Project description:We analyzed ten adenoid cystic carcinomas of head and neck by array-based comparative genomic hybridization (a-CGH) using DNA chips spotted 4,030 BAC clones. After data smoothing by the adaptive weights smoothing (AWS) procedure with the gain and loss analysis of DNA (GLAD) algorithm, a total of 89 DNA copy number aberrations (DSCNAs) were detected. The frequent (≥30%) DSCNAs were loss of 6q24, 6q25, 8p23, 6q25, and 6q23 and gains of 6q23, 8p23, 9p11-13, and 22q13. High-level gain was detected on 12q12-15 including MDM2 in two cases. These two cases showed immunohistochemically positive status of MDM2 and negative status of p53 and p21. Furthermore, the total number of DSCNAs was significantly greater in ACC with loss of 6q than in other ACC, in ACC without loss of 8p23 than in other ACC, and in ACC with 8p23 gain than in ACC with 8p23 loss, respectively. Though there is a limit in the evidence, a-CGH detected several candidate chromosomal imbalances associated with DSCNA accumulation in ACC. 6q loss, 12q gain aCGH DNA copy number aberrations screening in human cancer adenoid cystic carcinoma (ACC).
2011-08-31 | E-GEOD-22328 | biostudies-arrayexpress