Wu, S. et al. Circular ecDNA promotes accessible chromatin and high oncogene expression. Nature 575, 699–703 (2019).
Gorkin, D. U., Leung, D. & Ren, B. The 3D genome in transcriptional regulation and pluripotency. Cell Stem Cell 14, 762–775 (2014).
Zheng, H. & Xie, W. The role of 3D genome organization in development and cell differentiation. Nat. Rev. Mol. Cell Biol. 20, 535–550 (2019).
Bailey, C., Shoura, M. J., Mischel, P. S. & Swanton, C. Extrachromosomal DNA—relieving heredity constraints, accelerating tumour evolution. Ann. Oncol. 31, 884–893 (2020).
Kim, H. et al. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nat. Genet. 52, 891–897 (2020).
Turner, K. M. et al. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature 543, 122–125 (2017).
Verhaak, R. G. W., Bafna, V. & Mischel, P. S. Extrachromosomal oncogene amplification in tumour pathogenesis and evolution. Nat. Rev. Cancer 19, 283–288 (2019).
Cox, D., Yuncken, C. & Spriggs, A. I. Minute chromatin bodies in malignant tumours of childhood. Lancet 286, 55–58 (1965).
van der Bliek, A. M., Lincke, C. R. & Borst, P. Circular DNA of 3T6R50 double minute chromosomes. Nucleic Acids Res. 16, 4841–4851 (1988).
Hamkalo, B. A., Farnham, P. J., Johnston, R. & Schimke, R. T. Ultrastructural features of minute chromosomes in a methotrexate-resistant mouse 3T3 cell line. Proc. Natl Acad. Sci. 82, 1126–1130 (1985).
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).
VanDevanter, D. R., Piaskowski, V. D., Casper, J. T., Douglass, E. C. & Von Hoff, D. D. Ability of circular extrachromosomal DNA molecules to carry amplified MYCN protooncogenes in human neuroblastomas in vivo. J Natl Cancer Inst. 82, 1815–1821 (1990).
Nathanson, D. A. et al. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343, 72–76 (2014).
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).
Vicario, R. et al. Patterns of HER2 gene amplification and response to anti-HER2 therapies. PLoS ONE 10, e0129876 (2015).
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).
Kitajima, K., Haque, M., Nakamura, H., Hirano, T. & Utiyama, H. Loss of irreversibility of granulocytic differentiation induced by dimethyl sulfoxide in HL-60 sublines with a homogeneously staining region. Biochem. Biophys. Res. Commun. 288, 1182–1187 (2001).
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).
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).
Wahl, G. M. The importance of circular DNA in mammalian gene amplification. Cancer Res. 49, 1333–1340 (1989).
Kumar, P. et al. ATAC–seq identifies thousands of extrachromosomal circular DNA in cancer and cell lines. Sci. Adv. 6, eaba2489 (2020).
Morton, A. R. et al. Functional enhancers shape extrachromosomal oncogene amplifications. Cell 179, 1330–1341 (2019).
Helmsauer, K. et al. Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma. Nat. Commun. 11, 5823 (2020).
Itoh, N. & Shimizu, N. DNA replication-dependent intranuclear relocation of double minute chromatin. J. Cell Sci. 111, 3275–3285 (1998).
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).
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).
Beliveau, B. J. et al. Versatile design and synthesis platform for visualizing genomes with Oligopaint FISH probes. Proc. Natl Acad. Sci. USA 109, 21301–21306 (2012).
Koche, R. P. et al. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nat. Genetics 52, 29–34 (2019).
Parker, S. C. J. et al. Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants. Proc. Natl Acad. Sci. USA 110, 17921–17926 (2013).
Whyte, W. A. et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153, 307–319 (2013).
Lovén, J. et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153, 320–334 (2013).
Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010).
Sabari, B. R. et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science 361, eaar3958 (2018).
Ren, C. et al. Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth. Proc. Natl Acad. Sci. USA 115, 7949–7954 (2018).
Deshpande, V. et al. Exploring the landscape of focal amplifications in cancer using AmpliconArchitect. Nat. Commun. 10, 392 (2019).
Luebeck, J. et al. AmpliconReconstructor integrates NGS and optical mapping to resolve the complex structures of focal amplifications. Nat. Commun. 11, 4374 (2020).
Schwab, M., Klempnauer, K. H., Alitalo, K., Varmus, H. & Bishop, M. Rearrangement at the 5′ end of amplified c-myc in human COLO 320 cells is associated with abnormal transcription. Mol. Cell. Biol. 6, 2752–2755 (1986).
L’Abbate, A. et al. Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer. Nucleic Acids Res. 42, 9131–9145 (2014).
Hann, S. R., King, M. W., Bentley, D. L., Anderson, C. W. & Eisenman, R. N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt’s lymphomas. Cell 52, 185–195 (1988).
Carramusa, L. et al. The PVT-1 oncogene is a Myc protein target that is overexpressed in transformed cells. J. Cell. Physiol. 213, 511–518 (2007).
Cho, S. W. et al. Promoter of lncRNA gene PVT1 is a tumor-suppressor DNA boundary element. Cell 173, 1398–1412 (2018).
Tolomeo, D., Agostini, A., Visci, G., Traversa, D. & Storlazzi, C. T. PVT1: a long non-coding RNA recurrently involved in neoplasia-associated fusion transcripts. Gene 779, 145497 (2021).
Mumbach, M. R. et al. HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Nat. Methods 13, 919 (2016).
Fulco, C. P. et al. Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations. Nat. Genet. 51, 1664–1669 (2019).
Park, J. et al. A reciprocal regulatory circuit between CD44 and FGFR2 via c-myc controls gastric cancer cell growth. Oncotarget 7, 28670–28683 (2016).
Furlong, E. E. M. & Levine, M. Developmental enhancers and chromosome topology. Science 361, 1341–1345 (2018).
Zhu, Y. et al. Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription. Cancer Cell 39, 694–707 (2021).
Xue, K. S., Hooper, K. A., Ollodart, A. R., Dingens, A. S. & Bloom, J. D. Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture. Elife 5, e13974 (2016).
Vignuzzi, M., Stone, J. K., Arnold, J. J., Cameron, C. E. & Andino, R. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439, 344–348 (2006).
Henssen, A. et al. Targeting MYCN-driven transcription by BET-bromodomain inhibition. Clin. Cancer Res. 22, 2470–2481 (2016).
Xie, L. et al. 3D ATAC-PALM: super-resolution imaging of the accessible genome. Nat. Methods 17,430–436 (2020).
Ambros, P. F. et al. International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br. J. Cancer 100, 1471–1482 (2009).
Balaban-Malenbaum, G. & Gilbert, F. Double minute chromosomes and the homogeneously staining regions in chromosomes of a human neuroblastoma cell line. Science 198, 739–741 (1977).
Marrano, P., Irwin, M. S. & Thorner, P. S. Heterogeneity of MYCN amplification in neuroblastoma at diagnosis, treatment, relapse, and metastasis. Genes Chromosomes Cancer 56, 28–41 (2017).
Villamón, E. et al. Genetic instability and intratumoral heterogeneity in neuroblastoma with MYCN amplification plus 11q deletion. PLoS ONE 8, e53740 (2013).
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
Rajkumar, U. et al. EcSeg: semantic segmentation of metaphase images containing extrachromosomal DNA. Iscience 21, 428–435 (2019).
Veatch, S. L. et al. Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting. PLoS ONE 7, e31457 (2012).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114 (2014).
Ghandi, M. et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature 569, 503–508 (2019).
Normanno, D. et al. Probing the target search of DNA-binding proteins in mammalian cells using TetR as model searcher. Nat. Commun. 6, 7357 (2015).
Mirkin, E. V., Chang, F. S. & Kleckner, N. Protein-mediated chromosome pairing of repetitive arrays. J. Mol. Biol. 426, 550–557 (2014).
Grimm, J. B. et al. A general method to optimize and functionalize red-shifted rhodamine dyes. Nat. Methods 17, 815–821 (2020).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Zhang, Y. et al. Model-based analysis of ChIP–seq (MACS). Genome Biol. 9, R137 (2008).
Ramírez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
Sedlazeck, F. J. et al. Accurate detection of complex structural variations using single-molecule sequencing. Nat. Methods 15, 461–468 (2018).
Overhauser, J. in Pulsed-Field Gel Electrophoresis, Methods in Molecular Biology Vol. 12 (eds. Burmeister, M. & Ulanovsky, L.) 129–134 (Humana Press, 1992).
Picelli, S. et al. Tn5 transposase and tagmentation procedures for massively scaled sequencing projects. Genome Res. 24, 2033–2040 (2014).
Corces, M. R. et al. An improved ATAC–seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14, 959–962 (2017).
Talevich, E., Shain, A. H., Botton, T. & Bastian, B. C. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput. Biol. 12, e1004873 (2016).
Raeisi Dehkordi, S., Luebeck, J. & Bafna, V. FaNDOM: fast nested distance-based seeding of optical maps. Patterns 2, 100248 (2021).
Haas, B. J. et al. Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods. Genome Biol. 20, 213 (2019).
Hahne, F. & Ivanek, R. in Statistical Genomics, Methods in Molecular Biology Vol. 1418 (eds. Mathé, E. & Davis, S.) 335–351 (Humana Press, 2016).
Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).
Granja, J. M. et al. ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis. Nat. Genet. 53, 403–411 (2021).
Satpathy, A. T. et al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nat. Biotechnol. 37, 925–936 (2019).
Mumbach, M. R. et al. Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat. Genet. 49, 1602–1612 (2017).
Mumbach, M. R. et al. HiChIRP reveals RNA-associated chromosome conformation. Nat. Methods 16, 489–492 (2019).
Servant, N. et al. HiC-Pro: an optimized and flexible pipeline for Hi-C data processing. Genome Biol. 16, 259 (2015).
Bhattacharyya, S., Chandra, V., Vijayanand, P. & Ay, F. Identification of significant chromatin contacts from HiChIP data by FitHiChIP. Nat. Commun. 10, 4221 (2019).
Rao, S. S. P. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014).
Vidal, E. et al. OneD: increasing reproducibility of Hi-C samples with abnormal karyotypes. Nucleic Acids Res. 46, e49 (2018).
Flynn, R. A. et al. Discovery and functional interrogation of SARS-CoV-2 RNA–host protein interactions. Cell 184, 2394–2411 (2021).
Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol. 15, 554 (2014).
Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics 26, 589–595 (2010).
Scheinin, I. et al. DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly. Genome Res. 24, 2022–2032 (2014).
Hadi, K. et al. Distinct classes of complex structural variation uncovered across thousands of cancer genome graphs. Cell 183, 197–210 (2020).
Blumrich, A. et al. The FRA2C common fragile site maps to the borders of MYCN amplicons in neuroblastoma and is associated with gross chromosomal rearrangements in different cancers. Hum. Mol. Genet. 20, 1488–1501 (2011).
Gogolin, S. et al. CDK4 inhibition restores G1-S arrest in MYCN-amplified neuroblastoma cells in the context of doxorubicin-induced DNA damage. Cell Cycle 12, 1091–1104 (2013).
Durand, N. C. et al. Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments. Cell Syst. 3, 95–98 (2016).
Knight, P. A. & Ruiz, D. A fast algorithm for matrix balancing. IMA J. Numer. Anal. 33, 1029–1047 (2013).
Boeva, V. et al. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries. Nat. Genet. 49, 1408–1413 (2017).
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