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. Author manuscript; available in PMC: 2023 Jun 7.
Published in final edited form as: Nat Struct Mol Biol. 2022 Aug 10;29(8):736–744. doi: 10.1038/s41594-022-00806-7

Figure 2. ecDNA hubs drive oncogene expression and may shape cancer cell evolution.

Figure 2.

(a) ecDNA clustering in hubs is associated with oncogene transcription. (b) Enhancer-promoter contacts in trans within ecDNA hubs enable combinatorial interactions. (c) Enhancers and oncogenes may be co-selected on two levels. First, enhancer-oncogene pairs on the same molecule which drive oncogene expression can be selected together. Second, distinct ecDNA molecules containing enhancers and oncogenes that interact intermolecularly may be co-selected. (d) Dynamic ecDNA hub transcriptional activity is linked to heterogeneous oncogene expression levels in a cell population. (e) ecDNA hubs may allow correlated integration of multiple amplicon copies into chromosomes to form HSRs. (f) ecDNA-chromosome contacts allow enhancers on ecDNAs to interact with chromosomal genes and activate transcription.