An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma

DSpace/Manakin Repository

An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma

Citable link to this page

 

 
Title: An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma
Author: Drier, Yotam; Cotton, Matthew J.; Williamson, Kaylyn E.; Gillespie, Shawn M.; Ryan, Russell J.H.; Kluk, Michael J.; Carey, Christopher D.; Rodig, Scott J.; Sholl, Lynette M; Afrogheh, Amir H.; Faquin, William C.; Queimado, Lurdes; Qi, Jun; Wick, Michael J.; El-Naggar, Adel K.; Bradner, James E.; Moskaluk, Christopher A.; Aster, Jon C.; Knoechel, Birgit; Bernstein, Bradley E.

Note: Order does not necessarily reflect citation order of authors.

Citation: Drier, Y., M. J. Cotton, K. E. Williamson, S. M. Gillespie, R. J. Ryan, M. J. Kluk, C. D. Carey, et al. 2016. “An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma.” Nature genetics 48 (3): 265-272. doi:10.1038/ng.3502. http://dx.doi.org/10.1038/ng.3502.
Full Text & Related Files:
Abstract: 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.
Published Version: doi:10.1038/ng.3502
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767593/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002632
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters