|
| Status |
Public on Nov 24, 2021 |
| Title |
Exceptional response of high-risk neuroblastoma to RBM39 degrader Indisulam (ATAC-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Indisulam selectively bridges splicing factor RBM39 to DCAF15 for proteasomal degradation. However, clinical trials indicate that patient stratification based upon the mechanism of action of indisulam may be required to achieve the best response. Here we show that neuroblastoma, a MYC-driven cancer characterized by splicing dysregulation, requires RBM39 for survival, expresses high levels of DCAF15 among different solid tumor lineages, and is the most sensitive cancer lineage to indisulam that achieves therapeutic effect by specifically targeting RBM39 in neuroblastoma. Genetic depletion or proteasomal degradation of RBM39 by indisulam induces drastic splicing event changes in neuroblastoma cells. Through specifically targeting RBM39, indisulam induces exceptional tumor response in multiple high-risk neuroblastoma models. Collectively we demonstrate that high RBM39 dependency and high-level expression of DCAF15 provide indisulam a more efficacious therapeutic window to treating high-risk neuroblastoma.
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| |
|
| Overall design |
Examination of chromatin accessibility, histone modification in these indisulam resistant tumor derived cell lines.
|
| |
|
| Contributor(s) |
Fang J, Singh S, Jin H, Yang J |
| Citation(s) |
34788094 |
| |
| Submission date |
Jan 10, 2021 |
| Last update date |
Jun 06, 2025 |
| Contact name |
Hongjian Jin |
| E-mail(s) |
hongjian.jin@STJUDE.ORG
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Center for Applied Bioinformatics
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38015 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE164506 |
Exceptional response of high-risk neuroblastoma to RBM39 degrader Indisulam |
|
| Relations |
| BioProject |
PRJNA691027 |
| SRA |
SRP301119 |
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