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Series GSE70045 Query DataSets for GSE70045
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.
Overall design ChIP-Seq for H3K27ac and H3K27me3 in murine normal and EZH2 overexpressed tumor lung tissue
Contributor(s) Haikuo Z, Jun Q
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Submission date Jun 19, 2015
Last update date May 15, 2019
Contact name James Bradner
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)
GSM1716255 Lung_HZ1745_H3K27ac
GSM1716256 Lung_HZ1745_H3K27me3
GSM1716257 Lung_HZ1745_input
This SubSeries is part of SuperSeries:
GSE70047 Oncogenic deregulation of EZH2 as an opportunity for targeted therapy in lung cancer
BioProject PRJNA287535
SRA SRP059687

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Supplementary file Size Download File type/resource
GSE70045_RAW.tar 1.0 Gb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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