Cox, D., Yuncken, C. & Spriggs, A. I. Minute chromatin bodies in malignant tumours of childhood. Lancet 286, 55–58 (1965). The original description of ecDNA in tumor cells manifesting as small chromatin bodies on chromosome spreads.

Article  Google Scholar 

Spriggs, A. I., Boddington, M. M. & Clarke, C. M. Chromosomes of human cancer cells. Br. Med J. 2, 1431–1435 (1962).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Hoff, D. D. V., Needham-VanDevanter, D. R., Yucel, J., Windle, B. E. & Wahl, G. M. Amplified human MYC oncogenes localized to replicating submicroscopic circular DNA molecules. Proc. Natl Acad. Sci. USA 85, 4804–4808 (1988).

Article  Google Scholar 

Turner, K. M. et al. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature 543, 122–125 (2017). Systematic analysis of human cancer models using sequencing and cytogenetics identified ecDNAs in nearly half of human cancers and not in normal cells.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kim, H. et al. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nat. Genet. 52, 891–897 (2020). Comprehensive analysis of primary tumors found increased oncogene transcription and worsened outcomes linked to ecDNA.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kohl, N. E. et al. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 35, 359–367 (1983).

CAS  PubMed  Article  Google Scholar 

Benner, S., Wahl, G. & Hoff, D. V. Double minute chromosomes and homogeneously staining regions in tumors taken directly from patients versus in human tumor cell lines. Anti-cancer Drugs 2, 11–26 (1991).

CAS  PubMed  Article  Google Scholar 

Bigner, S. H., Mark, J. & Bigner, D. D. Cytogenetics of human brain tumors. Cancer Genet. Cytogenetics 47, 141–154 (1990).

CAS  Article  Google Scholar 

Storlazzi, C. T. et al. Gene amplification as double minutes or homogeneously staining regions in solid tumors: origin and structure. Genome Res. 20, 1198–1206 (2010).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Yoshimoto, M. et al. MYCN gene amplification: identification of cell populations containing double minutes and homogeneously staining regions in neuroblastoma tumors. Am. J. Pathol. 155, 1439–1443 (1999).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Vicario, R. et al. Patterns of HER2 gene amplification and response to anti-HER2 therapies. PLoS ONE 10, e0129876 (2015).

PubMed  PubMed Central  Article  CAS  Google Scholar 

McGill, J. R. et al. Double minutes are frequently found in ovarian carcinomas. Cancer Genet. Cytogenetics 71, 125–131 (1993).

CAS  Article  Google Scholar 

Lin, C. C. et al. Evolution of karyotypic abnormalities and C-MYC oncogene amplification in human colonic carcinoma cell lines. Chromosoma 92, 11–15 (1985).

CAS  PubMed  Article  Google Scholar 

Wahl, G. M. The importance of circular DNA in mammalian gene amplification. Cancer Res. 49, 1333–1340 (1989).

CAS  PubMed  Google Scholar 

Quinn, L. A., Moore, G. E., Morgan, R. T. & Woods, L. K. Cell lines from human colon carcinoma with unusual cell products, double minutes, and homogeneously staining regions. Cancer Res. 39, 4914–4924 (1979).

CAS  PubMed  Google Scholar 

Carroll, S. M. et al. Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol. Cell. Biol. 8, 1525–1533 (1988).

CAS  PubMed  PubMed Central  Google Scholar 

Maurer, B. J., Lai, E., Hamkalo, B. A., Hood, L. & Attardi, G. Novel submicroscopic extrachromosomal elements containing amplified genes in human cells. Nature 327, 434–437 (1987).

CAS  PubMed  Article  Google Scholar 

Pauletti, G., Lai, E. & Attardi, G. Early appearance and long-term persistence of the submicroscopic extrachromosomal elements (amplisomes) containing the amplified DHFR genes in human cell lines. Proc. Natl Acad. Sci. USA 87, 2955–2959 (1990).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Wang, Y. et al. eccDNAs are apoptotic products with high innate immunostimulatory activity. Nature 599, 308–314 (2021).

Møller, H. D. et al. Circular DNA elements of chromosomal origin are common in healthy human somatic tissue. Nat. Commun. 9, 1069 (2018).

PubMed  PubMed Central  Article  CAS  Google Scholar 

Møller, H. D., Parsons, L., Jørgensen, T. S., Botstein, D. & Regenberg, B. Extrachromosomal circular DNA is common in yeast. Proc. Natl Acad. Sci. USA 112, E3114–E3122 (2015).

Paulsen, T., Kumar, P., Koseoglu, M. M. & Dutta, A. Discoveries of extrachromosomal circles of DNA in normal and tumor cells. Trends Genet. 34, 270–278 (2018).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Wu, S. et al. Circular ecDNA promotes accessible chromatin and high oncogene expression. Nature 575, 699–703 (2019).

Hung, K. L. et al. ecDNA hubs drive cooperative intermolecular oncogene expression. Nature 600, 731–736 (2021). Discovery of ecDNA hubs that enable intermolecular activation of oncogene expression through enhancer–promoter interactions.

CAS  PubMed  PubMed Central  Google Scholar 

Levan, A. & Levan, G. Have double minutes functioning centromeres? Hereditas 88, 81–92 (1978). Conclusive evidence that ecDNAs lack centromeres, which explains their distinct mode of random segregation that results in copy-number heterogeneity.

CAS  PubMed  Article  Google Scholar 

Lundberg, G. et al. Binomial mitotic segregation of MYCN-carrying double minutes in neuroblastoma illustrates the role of randomness in oncogene amplification. PLoS ONE 3, e3099 (2008).

PubMed  PubMed Central  Article  CAS  Google Scholar 

Lange, J. T. et al. Principles of ecDNA random inheritance drive rapid genome change and therapy resistance in human cancers. Preprint at bioRxiv https://doi.org/10.1101/2021.06.11.447968 (2021).

Ståhl, F., Wettergren, Y. & Levan, G. Amplicon structure in multidrug-resistant murine cells: a nonrearranged region of genomic DNA corresponding to large circular DNA. Mol. Cell. Biol. 12, 1179–1187 (1992).

PubMed  PubMed Central  Google Scholar 

Nathanson, D. A. et al. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343, 72–76 (2014).

CAS  PubMed  Article  Google Scholar 

Yu, M. & Ren, B. The three-dimensional organization of mammalian genomes. Annu. Rev. Dev. Cell Biol. 33, 265–289 (2017).

Cremer, T. & Cremer, M. Chromosome territories. Cold Spring Harb. Perspect. Biol. 2, a003889 (2010).

PubMed  PubMed Central  Article  CAS  Google Scholar 

Spilianakis, C. G., Lalioti, M. D., Town, T., Lee, G. R. & Flavell, R. A. Interchromosomal associations between alternatively expressed loci. Nature 435, 637–645 (2005).

CAS  PubMed  Article  Google Scholar 

Apostolou, E. & Thanos, D. Virus infection induces NF-κB-dependent interchromosomal associations mediating monoallelic IFN-β gene expression. Cell 134, 85–96 (2008).

CAS  PubMed  Article  Google Scholar 

Maass, P. G., Barutcu, A. R. & Rinn, J. L. Interchromosomal interactions: a genomic love story of kissing chromosomes. J. Cell Biol. 218, 27–38 (2019).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Yi, E. et al. Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA hubs in cancer. Cancer Discov. 12, 468–483 (2021).

PubMed  PubMed Central  Article  Google Scholar 

Itoh, N. & Shimizu, N. DNA replication-dependent intranuclear relocation of double minute chromatin. J. Cell Sci. 111, 3275–3285 (1998).

CAS  PubMed  Article  Google Scholar 

Misteli, T. Beyond the sequence: cellular organization of genome function. Cell 128, 787–800 (2007).

CAS  PubMed  Article  Google Scholar 

Kanda, T., Sullivan, K. F. & Wahl, G. M. Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr. Biol. 8, 377–385 (1998).

CAS  PubMed  Article  Google Scholar 

Oobatake, Y. & Shimizu, N. Double-strand breakage in the extrachromosomal double minutes triggers their aggregation in the nucleus, micronucleation, and morphological transformation. Genes Chromosomes Cancer 59, 133–143 (2020).

CAS  PubMed  Article  Google Scholar 

Chong, S. et al. Imaging dynamic and selective low-complexity domain interactions that control gene transcription. Science 361, eaar2555 (2018).

Sabari, B. R. et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science 361, eaar3958 (2018).

PubMed  PubMed Central  Article  CAS  Google Scholar 

Gibson, B. A. et al. Organization of chromatin by intrinsic and regulated phase separation. Cell 179, 470–484 (2019).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Shin, Y. et al. Liquid nuclear condensates mechanically sense and restructure the genome. Cell 175, 1481–1491 (2018).

CAS  PubMed  PubMed Central  Article  Google Scholar 

Lovén, J. et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153, 320–334 (2013).