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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| Overall design |
Three biological replicates per treatment and time point were sequenced; ChIP libraries were isolated from individual replicates.
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| 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 |
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| Submission date |
Sep 13, 2019 |
| Last update date |
Feb 15, 2021 |
| Contact name |
Patrick Grohar |
| E-mail(s) |
groharp@email.chop.edu
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| Phone |
2674250494
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| Organization name |
Children's Hospital of Philadelphia
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| Street address |
3501 Civic Center Blvd
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| GSM4078562 |
BT12 cells, IPAc, mithramycin 8h_D, ChIP-seq |
| GSM4078563 |
BT12 cells, IPAc, mithramycin 8h_E, ChIP-seq |
| GSM4078564 |
BT12 cells, IPAc, mithramycin 8h_F, ChIP-seq |
| GSM4078565 |
BT12 cells, IPAc, mithramycin 18h_D, ChIP-seq |
| GSM4078566 |
BT12 cells, IPAc, mithramycin 18h_E, ChIP-seq |
| GSM4078567 |
BT12 cells, IPAc, mithramycin 18h_F, ChIP-seq |
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| This SubSeries is part of SuperSeries: |
| GSE137404 |
SWI/SNF inhibition leads to epigenetic reprogramming in rhabdoid tumor |
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| Relations |
| BioProject |
PRJNA565373 |
| SRA |
SRP221573 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE137399_RAW.tar |
8.8 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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