NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE142481 Query DataSets for GSE142481
Status Public on Jun 19, 2020
Title Combined targeting of the BRD4-NUT-p300 axis in NUT midline carcinoma by dual selective bromodomain inhibitor, NEO2734
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary NUT midline carcinoma (NMC) is a rare, aggressive subtype of squamous carcinoma that is driven by the BRD4-NUT fusion oncoprotein. BRD4, a BET protein, binds to chromatin through its two bromodomains, and NUT recruits the p300 histone acetyltransferse (HAT) to activate transcription of oncogenic target genes. BET selective bromodomain inhibitors have demonstrated on-target activity in NMC patients, but with limited efficacy. P300, like BRD4, contains a bromodomain. We show that combining selective p300/CBP and BET bromodomain inhibitors, GNE-781 and OTX015, respectively, induces synergistic inhibition of NMC growth. Treatment of NMC cells with the novel dual p300/CBP and BET bromodomain selective inhibitor, NEO2734, potently inhibits growth and induces differentiation of NMC cells in vitro; findings that correspond with potentiated transcriptional effects from combined BET and p300 bromodomain inhibition. In three disseminated NMC xenograft models, NEO2734 provided greater growth inhibition, with tumor regression and significant survival benefit seen in two of three models, compared with a lead clinical BET inhibitor or 'standard' chemotherapy.
 
Overall design High throughput analysis of ribosomal RNA depleted total RNA
 
Contributor(s) Morrison-Smith C, French CA
Citation(s) 32371576, 37645799
Submission date Dec 21, 2019
Last update date Sep 14, 2023
Contact name Chevaun Morrison-Smith
E-mail(s) cmorrison-smith@bwh.harvard.edu
Phone 6175254430
Organization name Brigham and Women's Hospital
Department Pathology
Lab Christopher French
Street address 77 AVENUE LOUIS PASTEUR, NRB 652
City BOSTON
State/province MA
ZIP/Postal code 02115-5727
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (20)
GSM4230230 DMSO 6h_797R1
GSM4230231 62.5 nM OTX-015 + 62.5 nM GNE-781 6h_797R1
GSM4230232 0.5 µM OTX-015 6h_797R1
Relations
BioProject PRJNA597130
SRA SRP238472

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE142481_PER403_797_CPM.txt.gz 1.7 Mb (ftp)(http) TXT
GSE142481_PER403_797_raw_counts.txt.gz 1.1 Mb (ftp)(http) TXT
GSE142481_RAW.tar 1.3 Gb (http)(custom) TAR (of TDF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap