|
| Status |
Public on Aug 11, 2018 |
| Title |
Retinoic acid suppresses MYB in adenoid cystic carcinoma [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Translocations that drive overexpression of the oncogenic transcription factor MYB are molecular hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor. Surgical resection, whenever possible, is the standard therapy for ACC, but there are no available therapeutic options available if surgery fails. Here we performed a chemical genetic screen using a zebrafish embryo culture system and identified retinoic acid agonists as potent suppressors of c-myb. Retinoic acid treatment strongly decreased c-myb gene expression in U937 cells and suggested a direct transcriptional mechanism of regulation. Retinoic acid agonists strongly inhibited tumor growth in vivo in different ACC patient derived xenograft models. Analysis of the xenografts revealed a significant decrease in MYB binding at translocated enhancers, thereby disrupting the MYB positive feedback loop that drives ACC. Our findings identify an important role of retinoic acid in MYB regulation and as a potential new effective therapy for ACC.
|
| |
|
| Overall design |
ChIP-seq analysis of myb, RAR, and H3K27ac in ACC xenograft samples treated with vehicle or ATRA
|
| |
|
| Contributor(s) |
Mandelbaum J, Zon LI |
| Citation(s) |
30209067 |
| |
| Submission date |
Apr 20, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Leonard Zon |
| E-mail(s) |
zon@enders.tch.harvard.edu
|
| Organization name |
Boston Children's Hospital
|
| Department |
Oncology/Hematology
|
| Street address |
1 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE98008 |
Retinoic acid suppresses MYB in adenoid cystic carcinoma |
|
| Relations |
| BioProject |
PRJNA383656 |
| SRA |
SRP104392 |
Less...
More...