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Series GSE134631 Query DataSets for GSE134631
Status Public on Jul 20, 2020
Title ARID1A Loss in Neuroblastoma Promotes the Adrenergic-to-Mesenchymal Transition by Regulating Enhancer-Mediated Gene Expression [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Gene mutations in components of SWI/SNF chromatin-remodeling complexes are found in approximately 20% of all human cancers, with ARID1A being the most frequently mutated subunit. In neuroblastoma, sequence alterations of ARID1A were identified in 6% of primary tumors and cell lines, and this gene is hemizygously deleted in at least 87% of cases with chromosome 1p deletion, which almost always accompanies MYCN gene amplification and is the most common deletions in high-risk subtypes of this tumor. However, the role of ARID1A haploinsufficiency in neuroblastoma pathogenesis and the mechanisms involved remain unclear. Here, we show that disruption of ARID1A homologs in a zebrafish model accelerates the onset and increases the penetrance of MYCN-driven neuroblastoma by increasing cell proliferation in the sympathoadrenal lineage. Depletion of ARID1A in human NGP neuroblastoma cells promoted the adrenergic-to-mesenchymal transition with changes in enhancer-mediated gene expression due to alterations in the genomic occupancies of two distinct SWI/SNF assemblies, BAF and PBAF. Our findings indicate that ARID1A is a haploinsufficient tumor suppressor in MYCN-driven neuroblastoma, whose depletion enhances tumor development and promotes the emergence of the more drug resistant mesenchymal cell state.
Overall design RNA-Seq for control and two ARID1A mutant NGP cells
Web link
Contributor(s) Shi H, Tao T, Abraham BJ, Durbin AD, Zimmerman MW, Kadoch C, Look AT
Citation(s) 32832616
Submission date Jul 22, 2019
Last update date Aug 25, 2020
Contact name Ting Tao
Organization name Children's Hospital, Zhejiang University School of Medicine
Lab Ting Tao
Street address 3333 Binsheng Road
City Hangzhou
State/province Zhejiang
ZIP/Postal code 310052
Country China
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (7)
GSM3959509 NGP_ctrl
GSM3959510 NGP_ARID1A_mut#1
GSM3959511 NGP_ARID1A_mut#2
This SubSeries is part of SuperSeries:
GSE134632 ARID1A Loss in Neuroblastoma Promotes the Adrenergic-to-Mesenchymal Transition by Regulating Enhancer-Mediated Gene Expression
BioProject PRJNA555892
SRA SRP215884

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
GSE134631_RAW.tar 2.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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