Genomics

Dataset Information

297

CDK7-dependent Transcriptional Addition in Basal-like Breast Cancer


ABSTRACT: Basal-like breast cancer (BBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that BBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that basal but not luminal breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. BBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of BBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in BBC and CDK7 inhibition may be useful therapy for this challenging cancer. ChIP-Seq for H3K27ac in basal-like breast cancer and luminal-like breast cancer cell lines

ORGANISM(S): Homo sapiens  

SUBMITTER: Nicholas Kwiatkowski   Brian J Abraham  Nathanael S Gray  Jean Zhao  Yubao Wang  Tong I Lee  Richard A Young 

PROVIDER: E-GEOD-65201 | ArrayExpress | 2015-01-23

SECONDARY ACCESSION(S): SRP052748GSE65201PRJNA273393

REPOSITORIES: GEO, ArrayExpress, ENA

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