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| Status |
Public on Jul 20, 2020 |
| Title |
ARID1A Loss in Neuroblastoma Promotes the Adrenergic-to-Mesenchymal Transition by Regulating Enhancer-Mediated Gene Expression [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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.
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| Overall design |
ChIP-Seq for SS18, ARID2, BRG1, H3K4Me3 and H3K27Ac in control and two ARID1A mutant NGP cells
|
| Web link |
https://doi.org/10.1126/sciadv.aaz3440
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| |
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| 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 |
| E-mail(s) |
[email protected]
|
| 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 (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE134632 |
ARID1A Loss in Neuroblastoma Promotes the Adrenergic-to-Mesenchymal Transition by Regulating Enhancer-Mediated Gene Expression |
|
| Relations |
| BioProject |
PRJNA555886 |
| SRA |
SRP215883 |
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