Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

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 demonstrated downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Function

ORGANISM(S): Homo sapiens

SUBMITTER: Gabriela Alexe 

PROVIDER: E-GEOD-43392 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress