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| Status |
Public on Feb 01, 2016 |
| Title |
An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Translocation events are frequent in cancer and may create chimeric fusions or ‘regulatory rearrangements’ that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps reveal distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Remarkably, MYB protein binds to the translocated enhancers, creating a positive feedback loop that sustains its expression. MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. Bromodomain inhibitors slow tumor growth in ACC primagraft models in vivo. Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in the alternate ACC lineages.
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| |
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| Overall design |
Examination of histone modifications in primary ACCs and primagrafts, MYB, BRD4, and P63 mapping in ACC primagrafts, H3K27ac of ACC cell line
Raw files have been deposited at the European Genome-phenome Archive (EGA), which is hosted by the EBI, under accession number EGAS00001001457.
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| |
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| Contributor(s) |
Drier Y, Knoechel B, Bernstein BE |
| Citation(s) |
26829750 |
| Submission date |
Jan 03, 2016 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Yotam Drier |
| E-mail(s) |
yotam.drier@mail.huji.ac.il
|
| Organization name |
The Hebrew University of Jerusalem
|
| Department |
Immunology and Cancer Research
|
| Lab |
Drier
|
| Street address |
Faculty of Medicine, The Hebrew University, Ein Kerem
|
| City |
Jerusalem |
| State/province |
Israel |
| ZIP/Postal code |
9112102 |
| Country |
Israel |
| |
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| Platforms (3) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (46)
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| Relations |
| BioProject |
PRJNA307509 |
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