GEO DataSets

Analysis of 5 MYC-amplified medulloblastoma cell lines treated with the BET bromodomain inhibitor JQ1. Cell lines derived from medulloblastoma patients. Results provide insight into the potential use of BET bromodomain inhibitors in the treatment of MYC-amplified medulloblastomas.

Organism:

Homo sapiens

Type:

Expression profiling by array, count, 2 agent, 5 cell line sets

Platform:

GPL6244

Series:

GSE51020

10 Samples

Download data: CEL

(Submitter supplied) MYC-amplified medulloblastomas are highly lethal tumors. BET bromodomain inhibition was recently described to downregulate MYC-associated transcriptional activity in various cancer subtypes. To investigate whether JQ1, a BET bromodomain inhibitor is downregulation MYC and MYC-associated transcriptional activity, we performed global gene expression profiling of five medulloblastomas MYC-amplified patient-derived cell lines treated by JQ1 and the inactive form of JQ1.

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS5346

Platform:

GPL6244

10 Samples

Download data: CEL

(Submitter supplied) The bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat induce synergistic anticancer effects We analyzed whether JQ1 and panobinostat synergistically modulate gene expression

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

12 Samples

Download data: CEL

(Submitter supplied) Two human acute lymphoblastic leukemia cell lines were treated with a BET bromodomain inhibitor that blocks BET association with chromatin. These cell lines, MHH-CALL4 and MUTZ-5, each carry translocation of the CRLF2 gene into the IgH locus, and their growth was found to be susceptible to BET inhibition. Gene expression changes were analyzed in each cell line versus vehicle control.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

24 Samples

Download data: CEL, CHP

(Submitter supplied) Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically-defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15207

12 Samples

Download data: CEL

(Submitter supplied) MYC genes are frequently amplified and correlate with poor prognosis in MB. BET bromodomains recognize acetylated lysine residues and often promote and maintain MYC transcription. Certain cyclin-dependent kinases (CDKs) are further known to support MYC stabilization in tumor cells. In this report, MB cells were suppressed by combined targeting of MYC expression and MYC stabilization using BET bromodomain inhibition and CDK2 inhibition, respectively. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL17301 GPL16331

50 Samples

Download data: TSV

(Submitter supplied) Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by early metastasis into lung and bone. Genetically, ES are defined by balanced chromosomal EWS/ETS translocations, which give rise to chimeric proteins (EWS-ETS) that generate an oncogenic transcriptional program associated with altered epigenetic marks throughout the genome. By use of an inhibitor (JQ1) blocking BET bromodomain binding proteins (BRDs) we strikingly observed a strong down-regulation of the predominant EWS-ETS protein EWS/FLI1 in a dose dependent manner. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

4 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL6244 GPL11154

28 Samples

Download data: BED, CEL, XLS

(Submitter supplied) We here use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

22 Samples

Download data: BED, XLS

(Submitter supplied) We here use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

6 Samples

Download data: CEL, XLS

(Submitter supplied) Bromodomain and extra terminal domain (BET) inhibition reduces occupancy of BET-family proteins at promoter and enhancer sites resulting in changes in the transcription of specific genes. We used microarray profiling to investigate the transcriptional changes induced by BET inhibitor JQ1 treatment in DV90 cells to identify the underlying changes of gene regulation that lead to JQ1 sensitivity.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17692

28 Samples

Download data: CEL

(Submitter supplied) Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

8 Samples

Download data: TXT

(Submitter supplied) The bromodomain and extra-terminal domain inhibitors (BETi) are promising epigenetic drugs for the treatment of various cancers through suppression of oncogenic transcription factors including MYC. However, only a subset of CRC cells response to BETi, suggesting an intrinsic resistance to BETi in CRC. We investigated the effect of JQ1 on cell proliferation, apoptosis, angiogenesis and MYC expression in a panel of 11 CRC cells in vitro and in vivo. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: XLSX

(Submitter supplied) Pathologic activation of c-Myc plays a central role in pathogenesis of several neoplasias, including multiple myeloma. However, therapeutic targeting of c-Myc has remained elusive due to its lack of a clear ligand-binding domain. We therefore targeted c-Myc transcriptional function by another means, namely the disruption of chromatin-dependent signal transduction. Members of the bromodomain and extra-terminal (BET) subfamily of human bromodomain proteins (BRD2, BRD3 and BRD4) associate with acetylated chromatin and facilitate transcriptional activation by increasing the effective molarity of recruited transcriptional activators. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

12 Samples

Download data: CEL

(Submitter supplied) We sequenced mRNA from 12 human cancer cell lines treated with DMSO or AZD5153 for 24h to determine compound mechanism of action

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

48 Samples

Download data: TXT

(Submitter supplied) To determine the global transcriptome changes in mantle cell lymphoma cells following treatment with the BET bromodomain antagonist, JQ1 Mantle Cell Lymphoma (MCL) cells exhibit increased B cell receptor and NFkB activities. The BET protein BRD4 is essential for the transcriptional activity of NFkB. Here, we demonstrate that treatment with the BET protein bromodomain antagonist (BA) JQ1 attenuates MYC and CDK4/6, inhibits the nuclear RelA levels and the expression of NFκB target genes including Bruton’s Tyrosine Kinase (BTK) in MCL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) Purpose: Osteosarcoma (OS) is the most common primary bone malignancy. OS consists of several subtypes including fibroblastic, osteoblastic and chondroblastic OS. We have developed genetically engineered mouse models of human OS that recapitulate two distinct subtypes, fibroblastic (Osx-CreLox p53-/- Rb-/-) and osteoblastic (Osx-Cre shRNA p53-/-) OS. The goal of this study was to identify transcriptional differences that distinguish the two subtypes. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: TXT

(Submitter supplied) The BET (bromodomain and extra terminal) protein family members including BRD4 bind to acetylated lysines on histones and regulate the expression of important oncogenes, e.g., MYC and BCL2. Here we demonstrate the sensitizing effects of the histone hyperacetylation inducing pan-histone deacetylase inhibitor (HDI) panobinostat (PS) on human AML blast progenitor cells (BPCs) to the BET protein inhibitor JQ1. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

2 Samples

Download data: CEL

(Submitter supplied) The MYC transcription factor is a master regulator of diverse cancer pathways and somatic cell reprogramming. MYC is a compelling therapeutic target that exhibits cancer-specific cellular effects. Pharmacologic inhibition of MYC function has proven challenging due to its numerous modes of forced expression and the difficulty of disrupting protein-DNA interactions. Here we demonstrate the rapid and potent abrogation of MYC gene transcription by representative small molecule bromodomain inhibitors of the BET family of chromatin adaptors. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

20 Samples

Download data: CEL, CHP

(Submitter supplied) In the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), NF-kappaB activity is essential for viability of the malignant cells and is sustained by constitutive activity of IkappaB kinase (IKK) in the cytoplasm. Here, we report an unexpected role for the bromodomain and extraterminal domain (BET) proteins BRD2 and BRD4 in maintaining oncogenic IKK activity in ABC DLBCL. IKK activity was reduced by small molecules targeting BET proteins as well as by genetic knockdown of BRD2 and BRD4 expression, thereby inhibiting downstream NF-kappaB-driven transcriptional programs and killing ABC DLBCL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL16699 GPL4133

12 Samples

Download data: TXT