EcDNA hubs drive cooperative intermolecular oncogene expression.

ABSTRACT: Extrachromosomal DNA (ecDNA) is prevalent in human cancers and mediates high expression of oncogenes through gene amplification and altered gene regulation¹. Gene induction typically involves cis-regulatory elements that contact and activate genes on the same chromosome^2,3. Here we show that ecDNA hubs-clusters of around 10-100 ecDNAs within the nucleus-enable intermolecular enhancer-gene interactions to promote oncogene overexpression. ecDNAs that encode multiple distinct oncogenes form hubs in diverse cancer cell types and primary tumours. Each ecDNA is more likely to transcribe the oncogene when spatially clustered with additional ecDNAs. ecDNA hubs are tethered by the bromodomain and extraterminal domain (BET) protein BRD4 in a MYC-amplified colorectal cancer cell

SUBMITTER: Hung KL 

PROVIDER: S-EPMC9126690 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature