|
| Status |
Public on Nov 01, 2015 |
| Title |
Oncogenic deregulation of EZH2 as an opportunity for targeted therapy in lung cancer [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
As a master regulator of chromatin structure and function, the EZH2 lysine methyltransferase orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non- small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 has proven elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with a new genetically-engineered mouse model of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor that arises from a facile synthesis and possesses improved pharmacologic properties. JQEZ5 promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a defined subset of lung cancer.
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| |
|
| Overall design |
ChIP-Seq for H3K27ac and H3K27me3 in murine normal and EZH2 overexpressed tumor lung tissue
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| |
|
| Contributor(s) |
Haikuo Z, Jun Q |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jun 19, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
James Bradner |
| E-mail(s) |
bradner_computation@dfci.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Bradner Lab
|
| Street address |
450 Brookline
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (12)
|
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| This SubSeries is part of SuperSeries: |
| GSE70047 |
Oncogenic deregulation of EZH2 as an opportunity for targeted therapy in lung cancer |
|
| Relations |
| BioProject |
PRJNA287535 |
| SRA |
SRP059687 |
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