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Research Articles

Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

Alexandre Puissant, Stacey M. Frumm, Gabriela Alexe, Christopher F. Bassil, Jun Qi, Yvan H. Chanthery, Erin A. Nekritz, Rhamy Zeid, William Clay Gustafson, Patricia Greninger, Matthew J. Garnett, Ultan McDermott, Cyril H. Benes, Andrew L. Kung, William A. Weiss, James E. Bradner and Kimberly Stegmaier
Alexandre Puissant
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Stacey M. Frumm
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Gabriela Alexe
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Christopher F. Bassil
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Jun Qi
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Yvan H. Chanthery
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Erin A. Nekritz
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Rhamy Zeid
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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William Clay Gustafson
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Patricia Greninger
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Matthew J. Garnett
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Ultan McDermott
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Cyril H. Benes
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Andrew L. Kung
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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William A. Weiss
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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James E. Bradner
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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Kimberly Stegmaier
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
Departments of 1Pediatric Oncology and 2Medical Oncology, Dana-Farber Cancer Institute; 3Boston Children's Hospital; 4Department of Medicine, Harvard Medical School; 5Bioinformatics Graduate Program, Boston University, Boston; 6The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge; 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts; 8Department of Pediatrics, Helen Diller Family Comprehensive Cancer Center; 9Departments of Neurology and Neurosurgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, California; and 10Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
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DOI: 10.1158/2159-8290.CD-12-0418 Published March 2013
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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 MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knockdown phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a significant survival advantage in 3 in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma.

Significance: Biomarkers of response to small-molecule inhibitors of BET bromodomains, a new compound class with promising anticancer activity, have been lacking. Here, we reveal MYCN amplification as a strong genetic predictor of sensitivity to BET bromodomain inhibitors, show a mechanistic rationale for this finding, and provide a translational framework for clinical trial development of BET bromodomain inhibitors for pediatric patients with MYCN-amplified neuroblastoma. Cancer Discov; 3(3); 308–23. ©2012 AACR.

See related commentary by Schnepp and Maris, p. 255

This article is highlighted in the In This Issue feature, p. 239

Footnotes

  • Note: Supplementary data for this article are available at Cancer Discovery Online (http://cancerdiscovery.aacrjournals.org/).

  • Received September 14, 2012.
  • Revision received December 4, 2012.
  • Accepted December 20, 2012.
  • 2012 American Association for Cancer Research.

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March 2013
Volume 3, Issue 3
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Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition
Alexandre Puissant, Stacey M. Frumm, Gabriela Alexe, Christopher F. Bassil, Jun Qi, Yvan H. Chanthery, Erin A. Nekritz, Rhamy Zeid, William Clay Gustafson, Patricia Greninger, Matthew J. Garnett, Ultan McDermott, Cyril H. Benes, Andrew L. Kung, William A. Weiss, James E. Bradner and Kimberly Stegmaier
Cancer Discov March 1 2013 (3) (3) 308-323; DOI: 10.1158/2159-8290.CD-12-0418

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Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition
Alexandre Puissant, Stacey M. Frumm, Gabriela Alexe, Christopher F. Bassil, Jun Qi, Yvan H. Chanthery, Erin A. Nekritz, Rhamy Zeid, William Clay Gustafson, Patricia Greninger, Matthew J. Garnett, Ultan McDermott, Cyril H. Benes, Andrew L. Kung, William A. Weiss, James E. Bradner and Kimberly Stegmaier
Cancer Discov March 1 2013 (3) (3) 308-323; DOI: 10.1158/2159-8290.CD-12-0418
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