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Series GSE137399 Query DataSets for GSE137399
Status Public on Nov 16, 2020
Title SWI/SNF inhibition leads to epigenetic reprogramming in rhabdoid tumor [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Rhabdoid tumor is a pediatric cancer characterized by the biallelic inactivation of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. SMARCB1 inactivation leads to SWI/SNF redistribution to favor a proliferative dedifferentiated cellular state. Although this deletion is the known oncogenic driver, SWI/SNF therapeutic targeting remains a challenge. Here we show mithramycin and a second-generation analogue EC-8042 are effective in this tumor type. Mithramycin evicts SWI/SNF from chromatin triggering a cellular response characterized by chromatin compartment remodeling and promoter reprogramming. These effects lead to differentiation and marked xenograft tumor regressions in vivo. This study provides a therapeutic candidate for rhabdoid tumor and an approach that may be applicable to the more than 20% of cancers characterized by mutated SWI/SNF.
Overall design Three biological replicates per treatment and time point were sequenced; ChIP libraries were isolated from individual replicates.
Contributor(s) Chasse MH, Grohar PJ, Johnson BK, TricheJr TJ
Citation(s) 33332735
NIH grant(s)
Grant ID Grant title Affiliation Name
F31 CA236300 Development of Mithramycin Analogues to Target Transcriptional Vulnerabilities in Rhabdoid Tumor VAN ANDEL RESEARCH INSTITUTE Maggie Chasse
Submission date Sep 13, 2019
Last update date Feb 15, 2021
Contact name Patrick Grohar
Phone 2674250494
Organization name Children's Hospital of Philadelphia
Street address 3501 Civic Center Blvd
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (9)
GSM4078559 BT12 cells, IPAc, Solv_D, ChIP-seq
GSM4078560 BT12 cells, IPAc, Solv_E, ChIP-seq
GSM4078561 BT12 cells, IPAc, Solv_F, ChIP-seq
This SubSeries is part of SuperSeries:
GSE137404 SWI/SNF inhibition leads to epigenetic reprogramming in rhabdoid tumor
BioProject PRJNA565373
SRA SRP221573

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Supplementary file Size Download File type/resource
GSE137399_RAW.tar 8.8 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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