GEO DataSets

(Submitter supplied) Global gene expression after CDK7 inhibition by THZ1

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16043

28 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:

GPL16043 GPL9052

46 Samples

Download data: BED, CEL

(Submitter supplied) ChIP-seq for Pol II, H3K27ac and H3K4me1 in neuroblastoma

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9052

18 Samples

Download data: BED

(Submitter supplied) The CDK7 inhibitor THZ1 has been shown to suppress MYCN gene transcription but not cause significant cell death as a single agent. The tyrosine kinase inhibitors (TKIs) ponatinib and lapatinib were found to exert synergistic anti-cancer effects in combination with the CDK7 inhibitor THZ1, on MYCN amplified neuroblastoma cell lines.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

6 Samples

Download data: CEL, XLSX

(Submitter supplied) Purpose: To assess THZ1-induced global changes of transcriptome of Hh-driven cancer Methods: SMB56 or SMB56-shSufu cells were mouse hedgehog-driven medulloblastoma cell lines that are either responsive or resistant to SMO inhibitor (GDC-0449). They were treated with 0.1 uM THZ1 or DMSO for 8 hours. 1 uM GDC-0449 treated SMB56 cells were included as control. Gene expression profiles were generated by RNAseq, in duplicate, using Hiseq3000. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL21273 GPL21493

10 Samples

Download data: XLSX

(Submitter supplied) Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signaling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TXT

(Submitter supplied) The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a paediatric cancer in which MYCN amplification is strongly associated with unfavourable outcome. Here, we show that CYC065, a clinical inhibitor of CDK2 and CDK9, selectively targets MYCN-amplified neuroblastoma via blockade of CDK9-dependent, MYCN-driven transcriptional elongation and CDK2-dependent proliferation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

30 Samples

Download data: TXT

(Submitter supplied) The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a paediatric cancer in which MYCN amplification is strongly associated with unfavourable outcome. Here, we show that CYC065, a clinical inhibitor of CDK2 and CDK9, selectively targets MYCN-amplified neuroblastoma via blockade of CDK9-dependent, MYCN-driven transcriptional elongation and CDK2-dependent proliferation. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

28 Samples

Download data: BEDGRAPH

(Submitter supplied) Neuroblastoma (NB) is a paediatric tumor wherein amplification of the oncogenic basic helix-loop-helix (bHLH) transcription factor (TF) MYCN confers clinical and biologic features prototypical of Myc-dependent cancers. TF-dependent cancers like MYCN-amplified NB are difficult to target, but the availability of clinical-candidate transcription inhibitors makes selective blockade of oncogenic TF activity a possibility. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: WIG

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone 3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using either bromodomain inhibition or CDK7 blockade. We observe that targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition and that DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL18573 GPL20301

26 Samples

Download data: BW, TXT

(Submitter supplied) We studied transcriptional changes by Illumina HumanHT-12 v4 microarrays in 2 Neuroblastoma cell lines after i-BET-726 treatment

Organism:

Homo sapiens

Type:

Expression profiling by array

Datasets:

GDS5364 GDS5365

Platform:

GPL10558

18 Samples

Download data: TXT

Analysis of SK-N-SH neuroblastoma (NB) cells treated with 0.1 or 1 uM I-BET726, a BET inhibitor. MYCN is unamplified in SK-N-SH. BET inhibitors display anti-proliferative activity in MYC driven hematologic cancer models. Results provide insight into the anti-proliferative activity of I-BET726 in NB.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 2 agent, 3 dose sets

Platform:

GPL10558

Series:

GSE47386

9 Samples

Download data

Analysis of CHP-212 neuroblastoma (NB) cells treated with 0.1 or 1 uM I-BET726, a BET inhibitor. MYCN is amplified in CHP-212. BET inhibitors display anti-proliferative activity in MYC driven hematologic cancer models. Results provide insight into the anti-proliferative activity of I-BET726 in NB.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 2 agent, 3 dose sets

Platform:

GPL10558

Series:

GSE47386

9 Samples

Download data

(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:

GPL16791 GPL15207

36 Samples

Download data: CEL, TAR

(Submitter supplied) Despite the development of diagnostic and advanced treatment strategies, the prognosis of patients with osteosarcoma remains poor. A limited understanding of the pathogenesis of osteosarcomas has impeded any improvement in patient outcomes over the past 4 decades. It is thus urgent to identify novel effective targets and treatment regimens for osteosarcoma patients. In this study we delineated the super-enhancer landscape in osteosarcoma cells on the basis of H3K27ac signal intensity by ChIP-Seq and found that super-enhancer-associated genes contribute to the malignant potential of osteosarcoma. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TAR

(Submitter supplied) CDK7 is a component of the general transcription factor IIH, which regulates RNAPII initiation and elongation.THZ2, a new molecular inhibitor, can completely inhibit the phosphorylation of the established intracellular CDK7 substrate RNAPII CTD at Ser-2, -5 and -7 through irreversible covalent binding to CDK7. Gene expression profiling was then performed to investigate the THZ2-induced transcription effect, and search the subset of sensitive genes in these 2 osteosarcoma cell lines.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15207

24 Samples

Download data: CEL

(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) Gene expression profiling were examined by Human HT-12 v4.0 Expression BeadChip arrays in SKBR3 and BT474 cells treated with HER2 inhibitor lapatinib or CDK7 inhibitor THZ1.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

18 Samples

Download data: IDAT

(Submitter supplied) Transcriptomic changes were compared by RNA-seq in human mammary epithelial cells (HMECs) with or without ectopic expression of oncogenic kinase HER2, PI3KCA(mut), or SHP(mut).

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TXT

(Submitter supplied) High-grade serous ovarian cancer is characterized by extensive copy number alterations, among which the amplification of MYC oncogene occurs in nearly half of tumors. We demonstrate that ovarian cancer cells highly depend on MYC for maintaining their oncogenic growth, indicating MYC as a therapeutic target for this difficult-to-treat malignancy. However, targeting MYC directly has proven difficult. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

12 Samples

Download data: TXT