@article{RN6083,
   author = {Wu, S. and Turner, K. M. and Nguyen, N. and Raviram, R. and Erb, M. and Santini, J. and Luebeck, J. and Rajkumar, U. and Diao, Y. and Li, B. and Zhang, W. and Jameson, N. and Corces, M. R. and Granja, J. M. and Chen, X. and Coruh, C. and Abnousi, A. and Houston, J. and Ye, Z. and Hu, R. and Yu, M. and Kim, H. and Law, J. A. and Verhaak, R. G. W. and Hu, M. and Furnari, F. B. and Chang, H. Y. and Ren, B. and Bafna, V. and Mischel, P. S.},
   title = {Circular ecDNA promotes accessible chromatin and high oncogene expression},
   journal = {Nature},
   volume = {575},
   number = {7784},
   pages = {699-703},
   note = {1476-4687
Wu, Sihan
Turner, Kristen M
Nguyen, Nam
Raviram, Ramya
Erb, Marcella
Santini, Jennifer
Luebeck, Jens
Rajkumar, Utkrisht
Diao, Yarui
Li, Bin
Zhang, Wenjing
Jameson, Nathan
Corces, M Ryan
Granja, Jeffrey M
Chen, Xingqi
Coruh, Ceyda
Abnousi, Armen
Houston, Jack
Ye, Zhen
Hu, Rong
Yu, Miao
Kim, Hoon
Law, Julie A
Verhaak, Roel G W
Hu, Ming
Furnari, Frank B
Chang, Howard Y
Ren, Bing
Bafna, Vineet
Mischel, Paul S
RM1 HG007735/HG/NHGRI NIH HHS/United States
P30 NS047101/NS/NINDS NIH HHS/United States
HHMI/Howard Hughes Medical Institute/United States
R01 NS073831/NS/NINDS NIH HHS/United States
NS73831/NH/NIH HHS/United States
GM114362/NH/NIH HHS/United States
P50 HG007735/HG/NHGRI NIH HHS/United States
R01 NS080939/NS/NINDS NIH HHS/United States
R35 CA209919/CA/NCI NIH HHS/United States
S10 OD023527/OD/NIH HHS/United States
R01 GM114362/GM/NIGMS NIH HHS/United States
R01 GM065490/GM/NIGMS NIH HHS/United States
T32 CA067754/CA/NCI NIH HHS/United States
T32 CA009523/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
2019/11/22
Nature. 2019 Nov;575(7784):699-703. doi: 10.1038/s41586-019-1763-5. Epub 2019 Nov 20.},
   abstract = {Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer(1,2), but our understanding of the structure of ecDNA and its effect on gene regulation is limited. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. Quantitative assessment of the chromatin state reveals that although ecDNA is packaged into chromatin with intact domain structure, it lacks higher-order compaction that is typical of chromosomes and displays significantly enhanced chromatin accessibility. Furthermore, ecDNA is shown to have a significantly greater number of ultra-long-range interactions with active chromatin, which provides insight into how the structure of circular ecDNA affects oncogene function, and connects ecDNA biology with modern cancer genomics and epigenetics.},
   keywords = {Cell Line, Tumor
Chromatin/chemistry/*genetics
DNA, Circular/genetics/*metabolism
Gene Expression Regulation, Neoplastic/*genetics
Humans
Microscopy, Electron, Scanning
Neoplasms/*genetics/physiopathology
Oncogenes/*genetics},
   ISSN = {0028-0836 (Print)
0028-0836},
   DOI = {10.1038/s41586-019-1763-5},
   year = {2019},
   type = {Journal Article}
}

{"_id":"5em5ePg7343Yyf4eB","bibbaseid":"wu-turner-nguyen-raviram-erb-santini-luebeck-rajkumar-etal-circularecdnapromotesaccessiblechromatinandhighoncogeneexpression-2019","author_short":["Wu, S.","Turner, K. M.","Nguyen, N.","Raviram, R.","Erb, M.","Santini, J.","Luebeck, J.","Rajkumar, U.","Diao, Y.","Li, B.","Zhang, W.","Jameson, N.","Corces, M. R.","Granja, J. M.","Chen, X.","Coruh, C.","Abnousi, A.","Houston, J.","Ye, Z.","Hu, R.","Yu, M.","Kim, H.","Law, J. A.","Verhaak, R. G. W.","Hu, M.","Furnari, F. B.","Chang, H. Y.","Ren, B.","Bafna, V.","Mischel, P. S."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Wu"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Turner"],"firstnames":["K.","M."],"suffixes":[]},{"propositions":[],"lastnames":["Nguyen"],"firstnames":["N."],"suffixes":[]},{"propositions":[],"lastnames":["Raviram"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Erb"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Santini"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Luebeck"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Rajkumar"],"firstnames":["U."],"suffixes":[]},{"propositions":[],"lastnames":["Diao"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Zhang"],"firstnames":["W."],"suffixes":[]},{"propositions":[],"lastnames":["Jameson"],"firstnames":["N."],"suffixes":[]},{"propositions":[],"lastnames":["Corces"],"firstnames":["M.","R."],"suffixes":[]},{"propositions":[],"lastnames":["Granja"],"firstnames":["J.","M."],"suffixes":[]},{"propositions":[],"lastnames":["Chen"],"firstnames":["X."],"suffixes":[]},{"propositions":[],"lastnames":["Coruh"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Abnousi"],"firstnames":["A."],"suffixes":[]},{"propositions":[],"lastnames":["Houston"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Ye"],"firstnames":["Z."],"suffixes":[]},{"propositions":[],"lastnames":["Hu"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Yu"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Kim"],"firstnames":["H."],"suffixes":[]},{"propositions":[],"lastnames":["Law"],"firstnames":["J.","A."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Hu"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Furnari"],"firstnames":["F.","B."],"suffixes":[]},{"propositions":[],"lastnames":["Chang"],"firstnames":["H.","Y."],"suffixes":[]},{"propositions":[],"lastnames":["Ren"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Bafna"],"firstnames":["V."],"suffixes":[]},{"propositions":[],"lastnames":["Mischel"],"firstnames":["P.","S."],"suffixes":[]}],"title":"Circular ecDNA promotes accessible chromatin and high oncogene expression","journal":"Nature","volume":"575","number":"7784","pages":"699-703","note":"1476-4687 Wu, Sihan Turner, Kristen M Nguyen, Nam Raviram, Ramya Erb, Marcella Santini, Jennifer Luebeck, Jens Rajkumar, Utkrisht Diao, Yarui Li, Bin Zhang, Wenjing Jameson, Nathan Corces, M Ryan Granja, Jeffrey M Chen, Xingqi Coruh, Ceyda Abnousi, Armen Houston, Jack Ye, Zhen Hu, Rong Yu, Miao Kim, Hoon Law, Julie A Verhaak, Roel G W Hu, Ming Furnari, Frank B Chang, Howard Y Ren, Bing Bafna, Vineet Mischel, Paul S RM1 HG007735/HG/NHGRI NIH HHS/United States P30 NS047101/NS/NINDS NIH HHS/United States HHMI/Howard Hughes Medical Institute/United States R01 NS073831/NS/NINDS NIH HHS/United States NS73831/NH/NIH HHS/United States GM114362/NH/NIH HHS/United States P50 HG007735/HG/NHGRI NIH HHS/United States R01 NS080939/NS/NINDS NIH HHS/United States R35 CA209919/CA/NCI NIH HHS/United States S10 OD023527/OD/NIH HHS/United States R01 GM114362/GM/NIGMS NIH HHS/United States R01 GM065490/GM/NIGMS NIH HHS/United States T32 CA067754/CA/NCI NIH HHS/United States T32 CA009523/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2019/11/22 Nature. 2019 Nov;575(7784):699-703. doi: 10.1038/s41586-019-1763-5. Epub 2019 Nov 20.","abstract":"Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer(1,2), but our understanding of the structure of ecDNA and its effect on gene regulation is limited. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. Quantitative assessment of the chromatin state reveals that although ecDNA is packaged into chromatin with intact domain structure, it lacks higher-order compaction that is typical of chromosomes and displays significantly enhanced chromatin accessibility. Furthermore, ecDNA is shown to have a significantly greater number of ultra-long-range interactions with active chromatin, which provides insight into how the structure of circular ecDNA affects oncogene function, and connects ecDNA biology with modern cancer genomics and epigenetics.","keywords":"Cell Line, Tumor Chromatin/chemistry/*genetics DNA, Circular/genetics/*metabolism Gene Expression Regulation, Neoplastic/*genetics Humans Microscopy, Electron, Scanning Neoplasms/*genetics/physiopathology Oncogenes/*genetics","issn":"0028-0836 (Print) 0028-0836","doi":"10.1038/s41586-019-1763-5","year":"2019","bibtex":"@article{RN6083,\n author = {Wu, S. and Turner, K. M. and Nguyen, N. and Raviram, R. and Erb, M. and Santini, J. and Luebeck, J. and Rajkumar, U. and Diao, Y. and Li, B. and Zhang, W. and Jameson, N. and Corces, M. R. and Granja, J. M. and Chen, X. and Coruh, C. and Abnousi, A. and Houston, J. and Ye, Z. and Hu, R. and Yu, M. and Kim, H. and Law, J. A. and Verhaak, R. G. W. and Hu, M. and Furnari, F. B. and Chang, H. Y. and Ren, B. and Bafna, V. and Mischel, P. S.},\n title = {Circular ecDNA promotes accessible chromatin and high oncogene expression},\n journal = {Nature},\n volume = {575},\n number = {7784},\n pages = {699-703},\n note = {1476-4687\nWu, Sihan\nTurner, Kristen M\nNguyen, Nam\nRaviram, Ramya\nErb, Marcella\nSantini, Jennifer\nLuebeck, Jens\nRajkumar, Utkrisht\nDiao, Yarui\nLi, Bin\nZhang, Wenjing\nJameson, Nathan\nCorces, M Ryan\nGranja, Jeffrey M\nChen, Xingqi\nCoruh, Ceyda\nAbnousi, Armen\nHouston, Jack\nYe, Zhen\nHu, Rong\nYu, Miao\nKim, Hoon\nLaw, Julie A\nVerhaak, Roel G W\nHu, Ming\nFurnari, Frank B\nChang, Howard Y\nRen, Bing\nBafna, Vineet\nMischel, Paul S\nRM1 HG007735/HG/NHGRI NIH HHS/United States\nP30 NS047101/NS/NINDS NIH HHS/United States\nHHMI/Howard Hughes Medical Institute/United States\nR01 NS073831/NS/NINDS NIH HHS/United States\nNS73831/NH/NIH HHS/United States\nGM114362/NH/NIH HHS/United States\nP50 HG007735/HG/NHGRI NIH HHS/United States\nR01 NS080939/NS/NINDS NIH HHS/United States\nR35 CA209919/CA/NCI NIH HHS/United States\nS10 OD023527/OD/NIH HHS/United States\nR01 GM114362/GM/NIGMS NIH HHS/United States\nR01 GM065490/GM/NIGMS NIH HHS/United States\nT32 CA067754/CA/NCI NIH HHS/United States\nT32 CA009523/CA/NCI NIH HHS/United States\nJournal Article\nResearch Support, N.I.H., Extramural\nResearch Support, Non-U.S. Gov't\nEngland\n2019/11/22\nNature. 2019 Nov;575(7784):699-703. doi: 10.1038/s41586-019-1763-5. Epub 2019 Nov 20.},\n abstract = {Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer(1,2), but our understanding of the structure of ecDNA and its effect on gene regulation is limited. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. Quantitative assessment of the chromatin state reveals that although ecDNA is packaged into chromatin with intact domain structure, it lacks higher-order compaction that is typical of chromosomes and displays significantly enhanced chromatin accessibility. 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W.","Hu, M.","Furnari, F. B.","Chang, H. Y.","Ren, B.","Bafna, V.","Mischel, P. 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