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Annual Review of Genomics and Human Genetics

Volume 23, 2022

Extrachromosomal DNA in Cancer

Abstract

In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive the formation and progression of tumors. ecDNA is a particularly challenging structural alteration. By untethering oncogenes from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, and results in treatment resistance. The profound changes in DNA shape and nuclear architecture generated by ecDNA alter the transcriptional landscape of tumors by catalyzing new types of regulatory interactions that do not occur on chromosomes. The current suite of tools for interrogating cancer genomes is well suited for deciphering sequence but has limited ability to resolve the complex changes in DNA structure and dynamics that ecDNA generates. Here, we review the challenges of resolving ecDNA form and function and discuss the emerging tool kit for deciphering ecDNA architecture and spatial organization, including what has been learned to date about how this dramatic change in shape alters tumor development, progression, and drug resistance.

Keyword(s): cancer, ecDNA, ecDNA evolution, ecDNA hubs, enhancer hijacking, homogeneously staining regions, HSRs
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/content/journals/10.1146/annurev-genom-120821-100535
2022-08-31
2024-05-15
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Literature Cited

  1. 1.
    Adelman K, Martin BJE. 2021. ecDNA party bus: bringing the enhancer to you.. Mol. Cell 81:1866–67
     [Google Scholar]
  2. 2.
    Akagi K, Li J, Broutian TR, Padilla-Nash H, Xiao W et al. 2014. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 24:185–99
     [Google Scholar]
  3. 3.
    Alitalo K, Schwab M, Lin CC, Varmus HE, Bishop JM. 1983. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. PNAS 80:1707–11
     [Google Scholar]
  4. 4.
    Alt FW, Kellems RE, Bertino JR, Schimke RT. 1978. Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells. J. Biol. Chem. 253:1357–70
     [Google Scholar]
  5. 5.
    Amler LC, Schwab M. 1989. Amplified N-myc in human neuroblastoma cells is often arranged as clustered tandem repeats of differently recombined DNA. Mol. Cell. Biol. 9:4903–13
     [Google Scholar]
  6. 6.
    Balaban-Malenbaum G, Gilbert F 1977. Double minute chromosomes and the homogeneously staining regions in chromosomes of a human neuroblastoma cell line. Science 198:739–41
     [Google Scholar]
  7. 7.
    Barker PE, Drwinga HL, Hittelman WN, Maddox AM. 1980. Double minutes replicate once during S phase of the cell cycle. Exp. Cell Res. 130:353–60
     [Google Scholar]
  8. 8.
    Beverley SM, Coderre JA, Santi DV, Schimke RT. 1984. Unstable DNA amplifications in methotrexate-resistant Leishmania consist of extrachromosomal circles which relocalize during stabilization. Cell 38:431–39
     [Google Scholar]
  9. 9.
    Biedler JL, Melera PW, Spengler BA. 1980. Specifically altered metaphase chromosomes in antifolate-resistant Chinese hamster cells that overproduce dihydrofolate reductase. Cancer Genet. Cytogenet. 2:47–60
     [Google Scholar]
  10. 10.
    Brown PC, Beverley SM, Schimke RT. 1981. Relationship of amplified dihydrofolate reductase genes to double minute chromosomes in unstably resistant mouse fibroblast cell lines. Mol. Cell. Biol. 1:1077–83
     [Google Scholar]
  11. 11.
    Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. 2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10:1213–18
     [Google Scholar]
  12. 12.
    Cameron DL, Baber J, Shale C, Valle-Inclan JE, Besselink N et al. 2021. GRIDSS2: comprehensive characterisation of somatic structural variation using single breakend variants and structural variant phasing. Genome Biol. 22:202
     [Google Scholar]
  13. 13.
    Carroll SM, DeRose ML, Gaudray P, Moore CM, Needham-Vandevanter DR et al. 1988. Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol. Cell. Biol. 8:1525–33
     [Google Scholar]
  14. 14.
    Chang HY, Nuyten DSA, Sneddon JB, Hastie T, Tibshirani R et al. 2005. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. PNAS 102:3738–43
     [Google Scholar]
  15. 15.
    Chang HY, Pannunzio NR, Adachi N, Lieber MR. 2017. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat. Rev. Mol. Cell Biol. 18:495–506
     [Google Scholar]
  16. 16.
    Chapman OS, Luebeck J, Wani S, Tiwari A, Pagadala M et al. 2021. The landscape of extrachromosomal circular DNA in medulloblastoma. bioRxiv 2021.10.18.464907. https://doi.org/10.1101/2021.10.18.464907
    [Crossref]
  17. 17.
    Chen X, Shen Y, Draper W, Buenrostro JD, Litzenburger U et al. 2016. ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing. Nat. Methods 13:1013–20
     [Google Scholar]
  18. 18.
    Corces MR, Trevino AE, Hamilton EG, Greenside PG, Sinnott-Armstrong NA et al. 2017. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14:959–62
     [Google Scholar]
  19. 19.
    Cox D, Yuncken C, Spriggs AI. 1965. Minute chromatin bodies in malignant tumours of childhood. Lancet 286:55–58
     [Google Scholar]
  20. 20.
    Cross R. 2020. The curious DNA circles that make treating cancer so hard. Chemical and Engineering News Oct. 18. https://cen.acs.org/pharmaceuticals/oncology/curious-DNA-circles-make-treating/98/i40
    [Google Scholar]
  21. 21.
    DeCarvalho AC, Kim H, Poisson LM, Winn ME, Mueller C et al. 2018. Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nat. Genet. 50:708–17
     [Google Scholar]
  22. 22.
    Deshpande V, Luebeck J, Nguyen NPD, Bakhtiari M, Turner KM et al. 2019. Exploring the landscape of focal amplifications in cancer using AmpliconArchitect. Nat. Commun. 10:392
     [Google Scholar]
  23. 23.
    Evans GA. 1993. Physical mapping of complex genomes US Patent 5,219,726
  24. 24.
    Fan Y, Mao R, Lv H, Xu J, Yan L et al. 2011. Frequency of double minute chromosomes and combined cytogenetic abnormalities and their characteristics. J. Appl. Genet. 52:53–59
     [Google Scholar]
  25. 25.
    Foulkes I, Sharpless NE. 2021. Cancer grand challenges: embarking on a new era of discovery. Cancer Discov. 11:23–27
     [Google Scholar]
  26. 26.
    Fungtammasan A, Walsh E, Chiaromonte F, Eckert KA, Makova KD. 2012. A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?. Genome Res. 22:993–1005. Corrigendum. 2016. Genome Res. 26:1451
     [Google Scholar]
  27. 27.
    Garsed D, Marshall O, Corbin V, Hsu A, Di Stefano L et al. 2014. The architecture and evolution of cancer neochromosomes. Cancer Cell 26:653–67
     [Google Scholar]
  28. 28.
    Haber DA, Beverley SM, Kiely ML, Schimke RT. 1981. Properties of an altered dihydrofolate reductase encoded by amplified genes in cultured mouse fibroblasts. J. Biol. Chem. 256:9501–10
     [Google Scholar]
  29. 29.
    Haber DA, Schimke RT. 1981. Unstable amplification of an altered dihydrofolate reductase gene associated with double-minute chromosomes. Cell 26:355–62
     [Google Scholar]
  30. 30.
    Hadi K, Yao X, Behr JM, Deshpande A, Xanthopoulakis C et al. 2020. Distinct classes of complex structural variation uncovered across thousands of cancer genome graphs. Cell 183:197–210
     [Google Scholar]
  31. 31.
    Hahn PJ, Nevaldine B, Longo JA. 1992. Molecular structure and evolution of double-minute chromosomes in methotrexate-resistant cultured mouse cells. Mol. Cell. Biol. 12:2911–18
     [Google Scholar]
  32. 32.
    Hamkalo BA, Farnham PJ, Johnston R, Schimke RT. 1985. Ultrastructural features of minute chromosomes in a methotrexate-resistant mouse 3T3 cell line. PNAS 82:1126–30
     [Google Scholar]
  33. 33.
    Helmsauer K, Valieva ME, Ali S, Chamorro González R, Schöpflin R et al. 2020. Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma. Nat. Commun. 11:5823
     [Google Scholar]
  34. 34.
    Hotta Y, Bassel A. 1965. Molecular size and circularity of DNA in cells of mammals and higher plants. PNAS 53:356–62
     [Google Scholar]
  35. 35.
    Hung K, Luebeck J, Dehkordi S, Coruh C, Law J et al. 2021. Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH. bioRxiv 2021.11.28.470285. https://doi.org/10.1101/2021.11.28.470285
    [Crossref]
  36. 36.
    Hung KL, Yost KE, Xie L, Shi Q, Helmsauer K et al. 2021. ecDNA hubs drive cooperative intermolecular oncogene expression. Nature 600:731–36
     [Google Scholar]
  37. 37.
    Inazawa J, Abe T, Inoue K, Nishigaki H, Horiike S et al. 1989. Simultaneous existence of double minute chromosomes and a homogeneously staining region in a retinoblastoma cell line (Y79) and amplification of N-myc at HSR. Cancer Genet. Cytogenet. 37:133–37
     [Google Scholar]
  38. 38.
    Int. Hum. Genome Seq. Consort. 2001. Initial sequencing and analysis of the human genome. Nature 409:860–921
     [Google Scholar]
  39. 39.
    Jaratlerdsiri W, Chan EKF, Petersen DC, Yang C, Croucher PI et al. 2017. Next generation mapping reveals novel large genomic rearrangements in prostate cancer. Oncotarget 8:23588–602
     [Google Scholar]
  40. 40.
    Kanda T, Sullivan KF, Wahl GM. 1998. Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr. Biol. 8:377–85
     [Google Scholar]
  41. 41.
    Kaufman RJ, Brown PC, Schimke RT. 1979. Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes. PNAS 76:5669–73
     [Google Scholar]
  42. 42.
    Kaufman RJ, Brown PC, Schimke RT. 1981. Loss and stabilization of amplified dihydrofolate reductase genes in mouse sarcoma S-180 cell lines. Mol. Cell. Biol. 1:1084–93
     [Google Scholar]
  43. 43.
    Kim H, Nguyen NP, Turner K, Wu S, Gujar AD et al. 2020. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nat. Genet. 52:891–97
     [Google Scholar]
  44. 44.
    Koche RP, Rodriguez-Fos E, Helmsauer K, Burkert M, MacArthur IC et al. 2020. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nat. Genet. 52:29–34
     [Google Scholar]
  45. 45.
    Kohl NE, Kanda N, Schreck RR, Bruns G, Latt SA et al. 1983. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 35:359–67
     [Google Scholar]
  46. 46.
    Koo DH, Molin WT, Saski CA, Jiang J, Putta K et al. 2018. Extrachromosomal circular DNA-based amplification and transmission of herbicide resistance in crop weed Amaranthus palmeri. PNAS 115:3332–37
     [Google Scholar]
  47. 47.
    Kucheria K. 1968. Double minute chromatin bodies in a sub-ependymal glioma. Br. J. Cancer 22:696–97
     [Google Scholar]
  48. 48.
    Kumar P, Dillon LW, Shibata Y, Jazaeri AA, Jones DR, Dutta A. 2017. Normal and cancerous tissues release extrachromosomal circular DNA (eccDNA) into the circulation. Mol. Cancer Res. 15:1197–205
     [Google Scholar]
  49. 49.
    L'Abbate A, Macchia G, D'Addabbo P, Lonoce A, Tolomeo D et al. 2014. Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer. Nucleic Acids Res. 42:9131–45
     [Google Scholar]
  50. 50.
    Lam ET, Hastie A, Lin C, Ehrlich D, Das SK et al. 2012. Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly. Nat. Biotechnol. 30:771–76
     [Google Scholar]
  51. 51.
    Lange JT, Chen CY, Pichugin Y, Xie L, Tang J et al. 2022. Principles of ecDNA random inheritance drive rapid genome change and therapy resistance in human cancers. Nat. Genet In press
  52. 52.
    Leung AK, Kwok TP, Wan R, Xiao M, Kwok PY et al. 2017. OMBlast: alignment tool for optical mapping using a seed-and-extend approach. Bioinformatics 33:311–19
     [Google Scholar]
  53. 53.
    Levan A, Levan G. 1978. Have double minutes functioning centromeres?. Hereditas 88:81–92
     [Google Scholar]
  54. 54.
    Li H, Durbin R. 2009. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–60
     [Google Scholar]
  55. 55.
    Lo AW, Sabatier L, Fouladi B, Pottier G, Ricoul M, Murnane JP. 2002. DNA amplification by breakage/fusion/bridge cycles initiated by spontaneous telomere loss in a human cancer cell line. Neoplasia 4:531–38
     [Google Scholar]
  56. 56.
    Long J, Shelhamer E, Darrell T. 2015. Fully convolutional networks for semantic segmentation. 2015 IEEE Conference on Computer Vision and Pattern Recognition3431–40 Piscataway, NJ: IEEE
     [Google Scholar]
  57. 57.
    Lubs HA, Salmon JH. 1965. The chromosomal complement of human solid tumors. II. Karyotypes of glial tumors. J. Neurosurg. 22:160–68
     [Google Scholar]
  58. 58.
    Luebeck J, Coruh C, Dehkordi SR, Lange JT, Turner KM et al. 2020. AmpliconReconstructor integrates NGS and optical mapping to resolve the complex structures of focal amplifications. Nat. Commun. 11:4374
     [Google Scholar]
  59. 59.
    Lundberg G, Rosengren AH, Håkanson U, Stewénius H, Jin Y et al. 2008. Binomial mitotic segregation of MYCN-carrying double minutes in neuroblastoma illustrates the role of randomness in oncogene amplification. PLOS ONE 3:e3099
     [Google Scholar]
  60. 60.
    Ly P, Brunner SF, Shoshani O, Kim DH, Lan W et al. 2019. Chromosome segregation errors generate a diverse spectrum of simple and complex genomic rearrangements. Nat. Genet. 51:705–15
     [Google Scholar]
  61. 61.
    Ly P, Cleveland DW. 2017. Rebuilding chromosomes after catastrophe: emerging mechanisms of chromothripsis. Trends Cell Biol. 27:917–30
     [Google Scholar]
  62. 62.
    Ly P, Teitz LS, Kim DH, Shoshani O, Skaletsky H et al. 2017. Selective Y centromere inactivation triggers chromosome shattering in micronuclei and repair by non-homologous end joining. Nat. Cell Biol. 19:68–75
     [Google Scholar]
  63. 63.
    Maass PG, Barutcu AR, Rinn JL. 2019. Interchromosomal interactions: a genomic love story of kissing chromosomes. J. Cell Biol. 218:27–38
     [Google Scholar]
  64. 64.
    Madhavi R, Guntur M, Ghosh R, Ghosh PK. 1990. Double minute chromosomes in the leukocytes of a young girl with breast carcinoma. Cancer Genet. Cytogenet. 44:203–7
     [Google Scholar]
  65. 65.
    Marotta M, Onodera T, Johnson J, Budd GT, Watanabe T et al. 2017. Palindromic amplification of the ERBB2 oncogene in primary HER2-positive breast tumors. Sci. Rep. 7:41921
     [Google Scholar]
  66. 66.
    Marshall OJ, Chueh AC, Wong LH, Choo KH. 2008. Neocentromeres: new insights into centromere structure, disease development, and karyotype evolution. Am. J. Hum. Genet. 82:261–82
     [Google Scholar]
  67. 67.
    McClintock B. 1932. A correlation of ring-shaped chromosomes with variegation in Zea mays. PNAS 18:672–81
     [Google Scholar]
  68. 68.
    McClintock B. 1939. The behavior in successive nuclear divisions of a chromosome broken at meiosis. PNAS 25:405–16
     [Google Scholar]
  69. 69.
    McClintock B. 1941. The stability of broken ends of chromosomes in Zea mays. Genetics 26:234–82
     [Google Scholar]
  70. 70.
    Meng X, Qi X, Guo H, Cai M, Li C et al. 2015. Novel role for non-homologous end joining in the formation of double minutes in methotrexate-resistant colon cancer cells. J. Med. Genet. 52:135–44
     [Google Scholar]
  71. 71.
    Mitra AB, Murty VV, Luthra UK. 1983. Double-minute chromosomes in the leukocytes of a patient with a previous history of cervical carcinoma. Cancer Genet. Cytogenet. 8:117–22
     [Google Scholar]
  72. 72.
    Molin WT, Yaguchi A, Blenner M, Saski CA. 2020. The eccDNA replicon: a heritable, extranuclear vehicle that enables gene amplification and glyphosate resistance in Amaranthus palmeri. Plant Cell 32:2132–40
     [Google Scholar]
  73. 73.
    Møller HD, Lin L, Xiang X, Petersen TS, Huang J et al. 2018. CRISPR-C: circularization of genes and chromosome by CRISPR in human cells. Nucleic Acids Res. 46:e131
     [Google Scholar]
  74. 74.
    Morton AR, Dogan-Artun N, Faber ZJ, MacLeod G, Bartels CF et al. 2019. Functional enhancers shape extrachromosomal oncogene amplifications. Cell 179:1330–41.e13
     [Google Scholar]
  75. 75.
    Mrasek K, Schoder C, Teichmann AC, Behr K, Franze B et al. 2010. Global screening and extended nomenclature for 230 aphidicolin-inducible fragile sites, including 61 yet unreported ones. Int. J. Oncol. 36:929–40
     [Google Scholar]
  76. 76.
    Müller HD. 2020. Circle-Seq: isolation and sequencing of chromosome-derived circular DNA elements in cells. Methods Mol. Biol. 2119:165–81
     [Google Scholar]
  77. 77.
    Nathanson DA, Gini B, Mottahedeh J, Visnyei K, Koga T et al. 2014. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343:72–76
     [Google Scholar]
  78. 78.
    Nulton TJ, Kim NK, DiNardo LJ, Morgan IM, Windle B. 2018. Patients with integrated HPV16 in head and neck cancer show poor survival. Oral Oncol. 80:52–55
     [Google Scholar]
  79. 79.
    Nulton TJ, Olex AL, Dozmorov M, Morgan IM, Windle B. 2017. Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma. Oncotarget 8:17684–99
     [Google Scholar]
  80. 80.
    Oobatake Y, Shimizu N. 2020. Double-strand breakage in the extrachromosomal double minutes triggers their aggregation in the nucleus, micronucleation, and morphological transformation. Genes Chromosomes Cancer 59:133–43
     [Google Scholar]
  81. 81.
    Pang J, Nguyen N, Luebeck J, Ball L, Finegersh A et al. 2021. Extrachromosomal DNA in HPV-mediated oropharyngeal cancer drives diverse oncogene transcription. Clin. Cancer Res. 27:6772–86
     [Google Scholar]
  82. 82.
    Paulsen T, Malapati P, Shibata Y, Wilson B, Eki R et al. 2021. MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage. Nucleic Acids Res. 49:11787–99
     [Google Scholar]
  83. 83.
    Paulsen T, Shibata Y, Kumar P, Dillon L, Dutta A 2019. Small extrachromosomal circular DNAs, microDNA, produce short regulatory RNAs that suppress gene expression independent of canonical promoters. Nucleic Acids Res. 47:4586–96
     [Google Scholar]
  84. 84.
    Raeisi Dehkordi S, Luebeck J, Bafna V 2021. FaNDOM: fast nested distance-based seeding of optical maps. Patterns 2:100248
     [Google Scholar]
  85. 85.
    Rajkumar U, Turner K, Luebeck J, Deshpande V, Chandraker M et al. 2019. EcSeg: semantic segmentation of metaphase images containing extrachromosomal DNA. iScience 21:428–35
     [Google Scholar]
  86. 86.
    Rao VK, Wangsa D, Robey RW, Huff L, Honjo Y et al. 2005. Characterization of ABCG2 gene amplification manifesting as extrachromosomal DNA in mitoxantrone-selected SF295 human glioblastoma cells. Cancer Genet. Cytogenet. 160:126–33
     [Google Scholar]
  87. 87.
    Raymond E, Faivre S, Weiss G, McGill J, Davidson K et al. 2001. Effects of hydroxyurea on extrachromosomal DNA in patients with advanced ovarian carcinomas. Clin. Cancer Res. 7:1171–80
     [Google Scholar]
  88. 88.
    Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD et al. 2001. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–33
     [Google Scholar]
  89. 89.
    Sanborn JZ, Salama SR, Grifford M, Brennan CW, Mikkelsen T et al. 2013. Double minute chromosomes in glioblastoma multiforme are revealed by precise reconstruction of oncogenic amplicons. Cancer Res. 73:6036–45
     [Google Scholar]
  90. 90.
    Scappaticci S, Fossati GS, Valenti L, Scabini M, Tateo S et al. 1995. A search for double minute chromosomes in cultured lymphocytes from different types of tumors. Cancer Genet. Cytogenet. 82:50–53
     [Google Scholar]
  91. 91.
    Schoenlein PV, Barrett JT, Kulharya A, Dohn MR, Sanchez A et al. 2003. Radiation therapy depletes extrachromosomally amplified drug resistance genes and oncogenes from tumor cells via micronuclear capture of episomes and double minute chromosomes. Int. J. Radiat. Oncol. Biol. Phys. 55:1051–65
     [Google Scholar]
  92. 92.
    Shale C, Baber J, Cameron DL, Wong M, Cowley MJ et al. 2020. Unscrambling cancer genomes via integrated analysis of structural variation and copy number. bioRxiv 2020.12.03.410860. https://doi.org/10.1101/2020.12.03.410860
    [Crossref]
  93. 93.
    Shimizu N, Itoh N, Utiyama H, Wahl GM. 1998. Selective entrapment of extrachromosomally amplified DNA by nuclear budding and micronucleation during S phase. J. Cell Biol. 140:1307–20
     [Google Scholar]
  94. 94.
    Shimizu N, Misaka N, Utani K. 2007. Nonselective DNA damage induced by a replication inhibitor results in the selective elimination of extrachromosomal double minutes from human cancer cells. Genes Chromosomes Cancer 46:865–74
     [Google Scholar]
  95. 95.
    Shimizu N, Shingaki K, Kaneko-Sasaguri Y, Hashizume T, Kanda T. 2005. When, where and how the bridge breaks: Anaphase bridge breakage plays a crucial role in gene amplification and HSR generation. Exp. Cell Res. 302:233–43
     [Google Scholar]
  96. 96.
    Shoshani O, Brunner SF, Yaeger R, Ly P, Nechemia-Arbely Y et al. 2021. Chromothripsis drives the evolution of gene amplification in cancer. Nature 591:137–41
     [Google Scholar]
  97. 97.
    Slade D. 2020. PARP and PARG inhibitors in cancer treatment. Genes Dev. 34:360–94
     [Google Scholar]
  98. 98.
    Smith CA, Vinograd J. 1972. Small polydisperse circular DNA of HeLa cells. J. Mol. Biol. 69:163–78
     [Google Scholar]
  99. 99.
    Smith G, Taylor-Kashton C, Dushnicky L, Symons S, Wright J, Mai S 2003. c-Myc-induced extrachromosomal elements carry active chromatin. Neoplasia 5:110–20
     [Google Scholar]
  100. 100.
    Snapka RM, Varshavsky A. 1983. Loss of unstably amplified dihydrofolate reductase genes from mouse cells is greatly accelerated by hydroxyurea. PNAS 80:7533–37
     [Google Scholar]
  101. 101.
    Song K, Minami JK, Huang A, Dehkordi SR, Lomeli SH et al. 2022. Plasticity of extrachromosomal and intrachromosomal BRAF amplifications in overcoming targeted therapy dosage challenges. Cancer Discov. 12:1046–69
     [Google Scholar]
  102. 102.
    Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR et al. 2011. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144:27–40
     [Google Scholar]
  103. 103.
    Storlazzi CT, Fioretos T, Surace C, Lonoce A, Mastrorilli A et al. 2006. MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene. Hum. Mol. Genet. 15:933–42
     [Google Scholar]
  104. 104.
    Storlazzi CT, Lonoce A, Guastadisegni MC, Trombetta D, D'Addabbo P et al. 2010. Gene amplification as double minutes or homogeneously staining regions in solid tumors: origin and structure. Genome Res. 20:1198–206
     [Google Scholar]
  105. 105.
    Takayama S, Uwaike Y. 1988. Analysis of the replication mode of double minutes using the PCC technique combined with BrdUrd labeling. Chromosoma 97:198–203
     [Google Scholar]
  106. 106.
    Tanaka T, Shimizu N. 2000. Induced detachment of acentric chromatin from mitotic chromosomes leads to their cytoplasmic localization at G1 and the micronucleation by lamin reorganization at S phase. J. Cell Sci. 113:697–707
     [Google Scholar]
  107. 107.
    Turner KM, Deshpande V, Beyter D, Koga T, Rusert J et al. 2017. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature 543:122–25
     [Google Scholar]
  108. 108.
    Tuzun E, Sharp AJ, Bailey JA, Kaul R, Morrison VA et al. 2005. Fine-scale structural variation of the human genome. Nat. Genet. 37:727–32
     [Google Scholar]
  109. 109.
    Umbreit NT, Zhang CZ, Lynch LD, Blaine LJ, Cheng AM et al. 2020. Mechanisms generating cancer genome complexity from a single cell division error. Science 368:eaba0712
     [Google Scholar]
  110. 110.
    Venter JC, Adams MD, Myers EW, Li PW, Mural RJ et al. 2001. The sequence of the human genome. Science 291:1304–51
     [Google Scholar]
  111. 111.
    Vogt N, Gibaud A, Lemoine F, de la Grange P, Debatisse M, Malfoy B. 2014. Amplicon rearrangements during the extrachromosomal and intrachromosomal amplification process in a glioma. Nucleic Acids Res. 42:13194
     [Google Scholar]
  112. 112.
    Vogt N, Lefère SH, Apiou F, Dutrillaux AM, Cör A et al. 2004. Molecular structure of double-minute chromosomes bearing amplified copies of the epidermal growth factor receptor gene in gliomas. PNAS 101:11368–73
     [Google Scholar]
  113. 113.
    Von Hoff DD, Forseth B, Clare CN, Hansen KL, VanDevanter D. 1990. Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells. J. Clin. Investig. 85:1887–95
     [Google Scholar]
  114. 114.
    Von Hoff DD, Waddelow T, Forseth B, Davidson K, Scott J, Wahl G. 1991. Hydroxyurea accelerates loss of extrachromosomally amplified genes from tumor cells. Cancer Res. 51:6273–79
     [Google Scholar]
  115. 115.
    Voullaire L, Saffery R, Davies J, Earle E, Kalitsis P et al. 1999. Trisomy 20p resulting from inverted duplication and neocentromere formation. Am. J. Med. Genet. 85:403–8
     [Google Scholar]
  116. 116.
    Voullaire LE, Slater HR, Petrovic V, Choo KH. 1993. A functional marker centromere with no detectable alpha-satellite, satellite III, or CENP-B protein: activation of a latent centromere?. Am. J. Hum. Genet. 52:1153–63
     [Google Scholar]
  117. 117.
    Wang Y, Wang M, Djekidel MN, Chen H, Liu D et al. 2021. eccDNAs are apoptotic products with high innate immunostimulatory activity. Nature 599:308–14
     [Google Scholar]
  118. 118.
    Wu S, Turner KM, Nguyen N, Raviram R, Erb M et al. 2019. Circular ecDNA promotes accessible chromatin and high oncogene expression. Nature 575:699–703
     [Google Scholar]
  119. 119.
    Xu K, Ding L, Chang TC, Shao Y, Chiang J et al. 2019. Structure and evolution of double minutes in diagnosis and relapse brain tumors. Acta Neuropathol. 137:123–37
     [Google Scholar]
  120. 120.
    Yan Y, Guo G, Huang J, Gao M, Zhu Q et al. 2020. Current understanding of extrachromosomal circular DNA in cancer pathogenesis and therapeutic resistance. J. Hematol. Oncol. 13:124
     [Google Scholar]
  121. 121.
    Yang L, Luquette LJ, Gehlenborg N, Xi R, Haseley PS et al. 2013. Diverse mechanisms of somatic structural variations in human cancer genomes. Cell 153:919–29
     [Google Scholar]
  122. 122.
    Yi E, Gujar AD, Guthrie M, Kim H, Zhao D et al. 2022. Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA hubs in cancer. Cancer Discov. 12:468–83
     [Google Scholar]
  123. 123.
    Yu L, Zhao Y, Quan C, Ji W, Zhu J et al. 2013. Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells. PLOS ONE 8:e71988
     [Google Scholar]
  124. 124.
    Zakov S, Kinsella M, Bafna V. 2013. An algorithmic approach for breakage-fusion-bridge detection in tumor genomes. PNAS 110:5546–51
     [Google Scholar]
  125. 125.
    Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK et al. 2015. Chromothripsis from DNA damage in micronuclei. Nature 522:179–84
     [Google Scholar]
  126. 126.
    Zhu Y, Gujar AD, Wong CH, Tjong H, Ngan CY et al. 2021. Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription. Cancer Cell 39:694–707
     [Google Scholar]
/content/journals/10.1146/annurev-genom-120821-100535
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Extrachromosomal DNA in Cancer
Annual Review of Genomics and Human Genetics 23, 29 (2022); https://doi.org/10.1146/annurev-genom-120821-100535
/content/journals/10.1146/annurev-genom-120821-100535
/content/journals/10.1146/annurev-genom-120821-100535
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  • Article Type: Review Article

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