Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition
Broad Institute · Boston University · +8 more institutions
Abstract
Abstract Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis showed downregulation of the…
Citation impact
- FWCI
- 30.36
- Percentile
- 100%
- References
- 53
Authors
17- APAlexandre Puissant
Broad Institute, Boston University, Boston Children's Hospital, Harvard University, Wellcome Sanger Institute, Massachusetts General Hospital, Dana-Farber Cancer Institute, Boston Children's Museum, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology
- SMStacey M. Frumm
Broad Institute, Boston University, Boston Children's Hospital, Harvard University, Wellcome Sanger Institute, Massachusetts General Hospital, Dana-Farber Cancer Institute, Boston Children's Museum, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology
- GAGabriela Alexe
Broad Institute, Boston University, Boston Children's Hospital, Harvard University, Wellcome Sanger Institute, Massachusetts General Hospital, Dana-Farber Cancer Institute, Boston Children's Museum, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology
- CFChristopher F. Bassil
Broad Institute, Boston University, Boston Children's Hospital, Harvard University, Wellcome Sanger Institute, Massachusetts General Hospital, Dana-Farber Cancer Institute, Boston Children's Museum, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology
- JQJun Qi
Broad Institute, Boston University, Boston Children's Hospital, Harvard University, Wellcome Sanger Institute, Massachusetts General Hospital, Dana-Farber Cancer Institute, Boston Children's Museum, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology
Topics & keywords
- Bromodomain
- Neuroblastoma
- BRD4
- Gene knockdown
- Cancer research
- Biology
- BET inhibitor
- Pediatric cancer
- Good health and well-being