@article{bc952cf3ea994e3b9149141506720408,
title = "Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription",
abstract = "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",
author = "Yanfen Zhu and Gujar, {Amit D} and Chee-Hong Wong and Harianto Tjong and Ngan, {Chew Yee} and Liang Gong and Yi-An Chen and Hoon Kim and Jihe Liu and Meihong Li and Adam Mil-Homens and Rahul Maurya and Chris Kuhlberg and Fanyue Sun and Eunhee Yi and deCarvalho, {Ana C} and Yijun Ruan and Verhaak, {Roel G W} and Chia-Lin Wei",
note = "Funding Information: The authors thank Drs. Edison Liu and Rachel Goldfeder for their feedback and comments on the manuscript, and Dr. Qianru Yu for her support in imaging analysis. Research reported in this publication was partially supported by the 4DN ( U54 DK107967 ) and ENCODE ( UM1 HG009409 ) consortia. C.-L.W., R.G.W.V., C.Y.N., and the research here are supported by NCI under award number P30CA034196 . Y.Z., L.G., and C.-L.W. are supported by grants from the US National Institutes of Health R01 GM127531 and R33 CA236681 . R.G.W.V. and A.D.G. are supported by grants from the US National Institutes of Health R01 CA190121 , R01 CA237208 , R21 NS114873 , the Musella Foundation and the B ∗ CURED Foundation , the Brain Tumour Charity , and the Department of Defense W81XWH1910246 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: The authors thank Drs. Edison Liu and Rachel Goldfeder for their feedback and comments on the manuscript, and Dr. Qianru Yu for her support in imaging analysis. Research reported in this publication was partially supported by the 4DN (U54 DK107967) and ENCODE (UM1 HG009409) consortia. C.-L.W. R.G.W.V. C.Y.N. and the research here are supported by NCI under award number P30CA034196. Y.Z. L.G. and C.-L.W. are supported by grants from the US National Institutes of Health R01 GM127531 and R33 CA236681. R.G.W.V. and A.D.G. are supported by grants from the US National Institutes of Health R01 CA190121, R01 CA237208, R21 NS114873, the Musella Foundation and the B?CURED Foundation, the Brain Tumour Charity, and the Department of Defense W81XWH1910246. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conceptualization, C.-L.W. R.G.W.V. Y.Z. A.D.G. and C.-H.W.; Methodology, Y.Z. A.D.G. C.-H.W. and H.T.; Software, C.-H.W. and H.T.; Formal analysis, Y.Z. C.-H.W. H.T. L.G. J.L. and H.K.; Investigation, Y.Z. A.D.G. C.Y.N. R.M. M.L. F.S. C.K. Y.-A.C. A.M.-H. and E.Y.; Resources, A.C.D.; Writing ? original draft, C.-L.W. R.G.W.V. Y.Z. A.D.G. C.-H.W. and H.T.; Writing ? review & editing, C.-L.W. R.G.W.V. Y.Z. A.D.G. C.-H.W. H.T. and Y.R.; Funding acquisition, C.-L.W. and R.G.W.V.; Supervision, C.-L.W. and R.G.W.V. R.G.W.V. is a co-founder of Boundless Bio, Inc (BB), and a member of its scientific advisory board. BB was not involved in the research presented here. C.-L.W. C.-H.W. H.T. and R.G.W.V. are co-inventors on a patent application (WO2020223309A1 ?Extrachromosomal DNA identification and methods of use?) submitted by The Jackson Laboratory. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = may,
day = "10",
doi = "https://doi.org/10.1016/j.ccell.2021.03.006",
language = "English",
volume = "39",
pages = "694--707.e7",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}