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Series GSE202859 Query DataSets for GSE202859
Status Public on Aug 03, 2023
Title Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Acquired resistance to tyrosine kinase inhibitors (TKI), such as osimertinib used to treat EGFR-mutant lung adenocarcinomas, limits long-term efficacy and is frequently caused by non-genetic mechanisms. Here, we define the chromatin accessibility and gene regulatory signatures of osimertinib sensitive and resistant EGFR-mutant cell and patient-derived models and uncover a role for mammalian SWI/SNF chromatin remodeling complexes in TKI resistance. By profiling mSWI/SNF genome-wide localization, we identify both shared and cancer cell line-specific gene targets underlying the resistant state. Importantly, genetic and pharmacologic disruption of the SMARCA4/SMARCA2 mSWI/SNF ATPases re-sensitizes a subset of resistant models to osimertinib via inhibition of mSWI/SNF-mediated regulation of cellular programs governing cell proliferation, epithelial-to-mesenchymal transition, epithelial cell differentiation, and NRF2 signaling. These data highlight the role of mSWI/SNF complexes in supporting TKI resistance and suggest potential utility of mSWI/SNF inhibitors in TKI-resistant lung cancers.
 
Overall design RNAseq data of sensitive and osimertinib resistant cell lines and after SMARCA4 knock-down and osimertinib treatment in PC9-OR and YU-005C cells.
Web link https://www.sciencedirect.com/science/article/pii/S1535610823002453?via%3Dihub#app2
 
Contributor(s) de Miguel FJ
Citation(s) 37541244
Submission date May 12, 2022
Last update date Aug 07, 2023
Contact name Fernando J. de Miguel
E-mail(s) fernando.demiguel@yale.edu
Organization name Yale University
Department Yale Cancer Center
Lab Politi Lab
Street address 333 Cedar Street
City New Haven
State/province Connecticut
ZIP/Postal code 06511
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (52)
GSM6134696 PC9 cells rep 1 (RNA-seq)
GSM6134697 PC9 cells rep 2 (RNA-seq)
GSM6134698 PC9 cells rep 3 (RNA-seq)
This SubSeries is part of SuperSeries:
GSE202864 Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
Relations
BioProject PRJNA837571

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
GSE202859_TPMs_allsamples.txt.gz 3.1 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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