| dc.contributor |
Koch Institute for Integrative Cancer Research at MIT |
|
| dc.creator |
Bandopadhayay, Pratiti |
|
| dc.creator |
Piccioni, Federica |
|
| dc.creator |
O’Rourke, Ryan |
|
| dc.creator |
Ho, Patricia |
|
| dc.creator |
Gonzalez, Elizabeth M. |
|
| dc.creator |
Buchan, Graham |
|
| dc.creator |
Qian, Kenin |
|
| dc.creator |
Gionet, Gabrielle |
|
| dc.creator |
Girard, Emily |
|
| dc.creator |
Coxon, Margo |
|
| dc.creator |
Rees, Matthew G. |
|
| dc.creator |
Brenan, Lisa |
|
| dc.creator |
Dubois, Frank |
|
| dc.creator |
Shapira, Ofer |
|
| dc.creator |
Greenwald, Noah F. |
|
| dc.creator |
Pages, Melanie |
|
| dc.creator |
Balboni Iniguez, Amanda |
|
| dc.creator |
Paolella, Brenton R. |
|
| dc.creator |
Meng, Alice |
|
| dc.creator |
Sinai, Claire |
|
| dc.creator |
Roti, Giovanni |
|
| dc.creator |
Dharia, Neekesh V. |
|
| dc.creator |
Creech, Amanda |
|
| dc.creator |
Tanenbaum, Benjamin |
|
| dc.creator |
Khadka, Prasidda |
|
| dc.creator |
Tracy, Adam |
|
| dc.creator |
Tiv, Hong L. |
|
| dc.creator |
Hong, Andrew L. |
|
| dc.creator |
Coy, Shannon |
|
| dc.creator |
Rashid, Rumana |
|
| dc.creator |
Lin, Jia-Ren |
|
| dc.creator |
Cowley, Glenn S. |
|
| dc.creator |
Lam, Fred Chiu-Lai |
|
| dc.creator |
Goodale, Amy |
|
| dc.creator |
Lee, Yenarae |
|
| dc.creator |
Schoolcraft, Kathleen |
|
| dc.creator |
Vazquez, Francisca |
|
| dc.creator |
Hahn, William C. |
|
| dc.creator |
Tsherniak, Aviad |
|
| dc.creator |
Bradner, James E. |
|
| dc.creator |
Yaffe, Michael B |
|
| dc.creator |
Milde, Till |
|
| dc.creator |
Pfister, Stefan M. |
|
| dc.creator |
Qi, Jun |
|
| dc.creator |
Schenone, Monica |
|
| dc.creator |
Carr, Steven A. |
|
| dc.creator |
Ligon, Keith L. |
|
| dc.creator |
Kieran, Mark W. |
|
| dc.creator |
Santagata, Sandro |
|
| dc.creator |
Olson, James M. |
|
| dc.creator |
Gokhale, Prafulla C. |
|
| dc.creator |
Jaffe, Jacob D. |
|
| dc.creator |
Root, David E. |
|
| dc.creator |
Stegmaier, Kimberly |
|
| dc.creator |
Johannessen, Cory M. |
|
| dc.creator |
Beroukhim, Rameen |
|
| dc.date |
2020-05-21T15:17:55Z |
|
| dc.date |
2020-05-21T15:17:55Z |
|
| dc.date |
2019-06 |
|
| dc.date |
2018-10 |
|
| dc.date |
2020-02-04T16:02:35Z |
|
| dc.date.accessioned |
2023-03-01T18:09:53Z |
|
| dc.date.available |
2023-03-01T18:09:53Z |
|
| dc.identifier |
2041-1723 |
|
| dc.identifier |
https://hdl.handle.net/1721.1/125375 |
|
| dc.identifier |
Bandopadhayay, P. et al. "Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma." Nature Communications 10, 1 (June 2019): 2400 © 2019 The Author(s) |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/278994 |
|
| dc.description |
BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms for its action, and ultimately for resistance, have not been fully defined. Here, using a combination of expression profiling, genome-scale CRISPR/Cas9-mediated loss of function and ORF/cDNA driven rescue screens, and cell-based models of spontaneous resistance, we identify bHLH/homeobox transcription factors and cell-cycle regulators as key genes mediating BETi’s response and resistance. Cells that acquire drug tolerance exhibit a more neuronally differentiated cell-state and expression of lineage-specific bHLH/homeobox transcription factors. However, they do not terminally differentiate, maintain expression of CCND2, and continue to cycle through S-phase. Moreover, CDK4/CDK6 inhibition delays acquisition of resistance. Therefore, our data provide insights about the mechanisms underlying BETi effects and the appearance of resistance and support the therapeutic use of combined cell-cycle inhibitors with BETi in MYC-amplified medulloblastoma. |
|
| dc.format |
application/pdf |
|
| dc.language |
en |
|
| dc.publisher |
Springer Science and Business Media LLC |
|
| dc.relation |
http://dx.doi.org/10.1038/s41467-019-10307-9 |
|
| dc.relation |
Nature Communications |
|
| dc.rights |
Creative Commons Attribution 4.0 International license |
|
| dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
|
| dc.source |
Nature |
|
| dc.title |
Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma |
|
| dc.type |
Article |
|
| dc.type |
http://purl.org/eprint/type/JournalArticle |
|