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Series GSE76465 Query DataSets for GSE76465
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.
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.
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
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
Platforms (3)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (46)
GSM2026067 X16_MYB
GSM2026068 X2_MYB
GSM2026069 X5M1_BRD4
BioProject PRJNA307509

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Supplementary file Size Download File type/resource
GSE76465_RAW.tar 8.7 Gb (http)(custom) TAR (of BED, TDF)
Processed data provided as supplementary file
Raw data not provided for this record

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