Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription

Cancer Cell. 2021 May 10;39(5):694-707.e7. doi: 10.1016/j.ccell.2021.03.006. Epub 2021 Apr 8.


Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. ecDNA-chromatin contact foci are characterized by broad and high-level H3K27ac signals converging predominantly on chromosomal genes of increased expression levels. Prostate cancer cells harboring synthetic ecDNA circles composed of characterized enhancers result in the genome-wide activation of chromosomal gene transcription. Deciphering the chromosomal targets of ecDNAs at single-molecule resolution reveals an association with actively expressed oncogenes spatially clustered within ecDNA-directed interaction networks. Our results suggest that ecDNA can function as mobile transcriptional enhancers to promote tumor progression and manifest a potential synthetic aneuploidy mechanism of transcription control in cancer.

Keywords: ChIA-Drop; ChIA-PET; chromatin interactions; ecDNA; mobile enhancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carcinogenesis / genetics
  • Chromatin / genetics
  • Chromosomes / genetics*
  • DNA, Neoplasm / genetics*
  • Glioblastoma / genetics*
  • Humans
  • Oncogenes / genetics*


  • Chromatin
  • DNA, Neoplasm