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Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes

View ORCID ProfileStefan C. Dentro, View ORCID ProfileIgnaty Leshchiner, View ORCID ProfileKerstin Haase, View ORCID ProfileMaxime Tarabichi, View ORCID ProfileJeff Wintersinger, View ORCID ProfileAmit G. Deshwar, View ORCID ProfileKaixian Yu, Yulia Rubanova, View ORCID ProfileGeoff Macintyre, View ORCID ProfileJonas Demeulemeester, Ignacio Vázquez-García, View ORCID ProfileKortine Kleinheinz, Dimitri G. Livitz, View ORCID ProfileSalem Malikic, Nilgun Donmez, View ORCID ProfileSubhajit Sengupta, Pavana Anur, View ORCID ProfileClemency Jolly, View ORCID ProfileMarek Cmero, View ORCID ProfileDaniel Rosebrock, View ORCID ProfileSteven Schumacher, Yu Fan, View ORCID ProfileMatthew Fittall, View ORCID ProfileRuben M. Drews, View ORCID ProfileXiaotong Yao, Juhee Lee, View ORCID ProfileMatthias Schlesner, View ORCID ProfileHongtu Zhu, David J. Adams, View ORCID ProfileGad Getz, View ORCID ProfilePaul C. Boutros, View ORCID ProfileMarcin Imielinski, Rameen Beroukhim, View ORCID ProfileS. Cenk Sahinalp, Yuan Ji, View ORCID ProfileMartin Peifer, View ORCID ProfileInigo Martincorena, View ORCID ProfileFlorian Markowetz, View ORCID ProfileVille Mustonen, Ke Yuan, View ORCID ProfileMoritz Gerstung, View ORCID ProfilePaul T. Spellman, Wenyi Wang, View ORCID ProfileQuaid D. Morris, View ORCID ProfileDavid C. Wedge, View ORCID ProfilePeter Van Loo, on behalf of the PCAWG Evolution and Heterogeneity Working Groupthe PCAWG consortium., the PCAWG consortium
doi: https://doi.org/10.1101/312041
Stefan C. Dentro
1The Francis Crick Institute, London, United Kingdom
2Wellcome Trust Sanger Institute, Cambridge, United Kingdom
3Big Data Institute, University of Oxford, Oxford, United Kingdom
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Ignaty Leshchiner
4Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Kerstin Haase
1The Francis Crick Institute, London, United Kingdom
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Maxime Tarabichi
1The Francis Crick Institute, London, United Kingdom
2Wellcome Trust Sanger Institute, Cambridge, United Kingdom
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Jeff Wintersinger
5University of Toronto, Toronto, Canada
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Amit G. Deshwar
5University of Toronto, Toronto, Canada
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Kaixian Yu
6The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Yulia Rubanova
5University of Toronto, Toronto, Canada
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Geoff Macintyre
7Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
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Jonas Demeulemeester
1The Francis Crick Institute, London, United Kingdom
8Department of Human Genetics, University of Leuven, Leuven, Belgium
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Ignacio Vázquez-García
2Wellcome Trust Sanger Institute, Cambridge, United Kingdom
9University of Cambridge, Cambridge, United Kingdom
10Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
11Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA
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Kortine Kleinheinz
12German Cancer Research Center (DKFZ), Heidelberg, Germany
13Heidelberg University, Heidelberg, Germany
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Dimitri G. Livitz
4Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Salem Malikic
14Simon Fraser University, Vancouver, Canada
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Nilgun Donmez
14Simon Fraser University, Vancouver, Canada
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Subhajit Sengupta
15NorthShore University HealthSystem, Evanston, IL, USA
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Pavana Anur
16Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA
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Clemency Jolly
1The Francis Crick Institute, London, United Kingdom
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Marek Cmero
17University of Melbourne, Melbourne, Australia
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Daniel Rosebrock
4Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Steven Schumacher
4Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Yu Fan
6The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Matthew Fittall
1The Francis Crick Institute, London, United Kingdom
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Ruben M. Drews
7Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
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Xiaotong Yao
18Weill Cornell Medicine, New York, NY, USA
19New York Genome Center, New York, NY, USA
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Juhee Lee
20University of California Santa Cruz, Santa Cruz, CA, USA
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Matthias Schlesner
10Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Hongtu Zhu
6The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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David J. Adams
2Wellcome Trust Sanger Institute, Cambridge, United Kingdom
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Gad Getz
4Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Paul C. Boutros
5University of Toronto, Toronto, Canada
21University of California, Los Angeles, Los Angeles, CA, USA
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Marcin Imielinski
18Weill Cornell Medicine, New York, NY, USA
19New York Genome Center, New York, NY, USA
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Rameen Beroukhim
4Broad Institute of MIT and Harvard, Cambridge, MA, USA
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S. Cenk Sahinalp
22Indiana University, Bloomington, IN, USA
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Yuan Ji
15NorthShore University HealthSystem, Evanston, IL, USA
23The University of Chicago, Chicago, IL, USA
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Martin Peifer
24University of Cologne, Cologne, Germany
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Inigo Martincorena
2Wellcome Trust Sanger Institute, Cambridge, United Kingdom
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Florian Markowetz
7Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
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Ville Mustonen
25Organismal and Evolutionary Biology Research Programme, Department of Computer Science, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
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Ke Yuan
7Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
26School of Computing Science, University of Glasgow, Glasgow, United Kingdom
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Moritz Gerstung
27European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, United Kingdom
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Paul T. Spellman
16Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA
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Wenyi Wang
6The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Quaid D. Morris
5University of Toronto, Toronto, Canada
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David C. Wedge
3Big Data Institute, University of Oxford, Oxford, United Kingdom
28Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom
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Peter Van Loo
1The Francis Crick Institute, London, United Kingdom
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  • For correspondence: Peter.VanLoo@crick.ac.uk
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Article Information

doi 
https://doi.org/10.1101/312041
History 
  • April 22, 2020.

Article Versions

  • Version 1 (May 5, 2018 - 15:25).
  • Version 2 (May 7, 2018 - 10:20).
  • Version 3 (May 12, 2018 - 13:15).
  • Version 4 (July 13, 2018 - 13:45).
  • You are viewing Version 5, the most recent version of this article.
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

Author Information

  1. Stefan C. Dentro1,2,3,#,
  2. Ignaty Leshchiner4,#,
  3. Kerstin Haase1,#,
  4. Maxime Tarabichi1,2,#,
  5. Jeff Wintersinger5,#,
  6. Amit G. Deshwar5,#,
  7. Kaixian Yu6,#,
  8. Yulia Rubanova5,#,
  9. Geoff Macintyre7,#,
  10. Jonas Demeulemeester1,8,#,
  11. Ignacio Vázquez-García2,9,10,11,
  12. Kortine Kleinheinz12,13,
  13. Dimitri G. Livitz4,
  14. Salem Malikic14,
  15. Nilgun Donmez14,
  16. Subhajit Sengupta15,
  17. Pavana Anur16,
  18. Clemency Jolly1,
  19. Marek Cmero17,
  20. Daniel Rosebrock4,
  21. Steven Schumacher4,
  22. Yu Fan6,
  23. Matthew Fittall1,
  24. Ruben M. Drews7,
  25. Xiaotong Yao18,19,
  26. Juhee Lee20,
  27. Matthias Schlesner10,
  28. Hongtu Zhu6,
  29. David J. Adams2,
  30. Gad Getz4,
  31. Paul C. Boutros5,21,
  32. Marcin Imielinski18,19,
  33. Rameen Beroukhim4,
  34. S. Cenk Sahinalp22,
  35. Yuan Ji15,23,
  36. Martin Peifer24,
  37. Inigo Martincorena2,
  38. Florian Markowetz7,
  39. Ville Mustonen25,
  40. Ke Yuan7,26,
  41. Moritz Gerstung27,
  42. Paul T. Spellman16,
  43. Wenyi Wang6,#,
  44. Quaid D. Morris5,#,
  45. David C. Wedge3,28,#,
  46. Peter Van Loo1,#,*,
  47. on behalf of the PCAWG Evolution and Heterogeneity Working Groupthe PCAWG consortium.29,
  48. the PCAWG consortium
  1. 1The Francis Crick Institute, London, United Kingdom
  2. 2Wellcome Trust Sanger Institute, Cambridge, United Kingdom
  3. 3Big Data Institute, University of Oxford, Oxford, United Kingdom
  4. 4Broad Institute of MIT and Harvard, Cambridge, MA, USA
  5. 5University of Toronto, Toronto, Canada
  6. 6The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  7. 7Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
  8. 8Department of Human Genetics, University of Leuven, Leuven, Belgium
  9. 9University of Cambridge, Cambridge, United Kingdom
  10. 10Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  11. 11Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA
  12. 12German Cancer Research Center (DKFZ), Heidelberg, Germany
  13. 13Heidelberg University, Heidelberg, Germany
  14. 14Simon Fraser University, Vancouver, Canada
  15. 15NorthShore University HealthSystem, Evanston, IL, USA
  16. 16Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA
  17. 17University of Melbourne, Melbourne, Australia
  18. 18Weill Cornell Medicine, New York, NY, USA
  19. 19New York Genome Center, New York, NY, USA
  20. 20University of California Santa Cruz, Santa Cruz, CA, USA
  21. 21University of California, Los Angeles, Los Angeles, CA, USA
  22. 22Indiana University, Bloomington, IN, USA
  23. 23The University of Chicago, Chicago, IL, USA
  24. 24University of Cologne, Cologne, Germany
  25. 25Organismal and Evolutionary Biology Research Programme, Department of Computer Science, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
  26. 26School of Computing Science, University of Glasgow, Glasgow, United Kingdom
  27. 27European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, United Kingdom
  28. 28Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom
  1. ↵*To whom correspondence may be addressed: Peter Van Loo, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, United Kingdom. Tel: +44 (0) 20 3796 1719, e-mail: Peter.VanLoo{at}crick.ac.uk.
  1. ↵# These authors contributed equally.

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Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
Stefan C. Dentro, Ignaty Leshchiner, Kerstin Haase, Maxime Tarabichi, Jeff Wintersinger, Amit G. Deshwar, Kaixian Yu, Yulia Rubanova, Geoff Macintyre, Jonas Demeulemeester, Ignacio Vázquez-García, Kortine Kleinheinz, Dimitri G. Livitz, Salem Malikic, Nilgun Donmez, Subhajit Sengupta, Pavana Anur, Clemency Jolly, Marek Cmero, Daniel Rosebrock, Steven Schumacher, Yu Fan, Matthew Fittall, Ruben M. Drews, Xiaotong Yao, Juhee Lee, Matthias Schlesner, Hongtu Zhu, David J. Adams, Gad Getz, Paul C. Boutros, Marcin Imielinski, Rameen Beroukhim, S. Cenk Sahinalp, Yuan Ji, Martin Peifer, Inigo Martincorena, Florian Markowetz, Ville Mustonen, Ke Yuan, Moritz Gerstung, Paul T. Spellman, Wenyi Wang, Quaid D. Morris, David C. Wedge, Peter Van Loo, on behalf of the PCAWG Evolution and Heterogeneity Working Groupthe PCAWG consortium., the PCAWG consortium
bioRxiv 312041; doi: https://doi.org/10.1101/312041
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Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
Stefan C. Dentro, Ignaty Leshchiner, Kerstin Haase, Maxime Tarabichi, Jeff Wintersinger, Amit G. Deshwar, Kaixian Yu, Yulia Rubanova, Geoff Macintyre, Jonas Demeulemeester, Ignacio Vázquez-García, Kortine Kleinheinz, Dimitri G. Livitz, Salem Malikic, Nilgun Donmez, Subhajit Sengupta, Pavana Anur, Clemency Jolly, Marek Cmero, Daniel Rosebrock, Steven Schumacher, Yu Fan, Matthew Fittall, Ruben M. Drews, Xiaotong Yao, Juhee Lee, Matthias Schlesner, Hongtu Zhu, David J. Adams, Gad Getz, Paul C. Boutros, Marcin Imielinski, Rameen Beroukhim, S. Cenk Sahinalp, Yuan Ji, Martin Peifer, Inigo Martincorena, Florian Markowetz, Ville Mustonen, Ke Yuan, Moritz Gerstung, Paul T. Spellman, Wenyi Wang, Quaid D. Morris, David C. Wedge, Peter Van Loo, on behalf of the PCAWG Evolution and Heterogeneity Working Groupthe PCAWG consortium., the PCAWG consortium
bioRxiv 312041; doi: https://doi.org/10.1101/312041

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