Contradictory Results
Neutral tumor evolution?
Maxime Tarabichi, Iñigo Martincorena, Moritz Gerstung, Florian Markowetz, Paul T. Spellman, Quaid D. Morris, Ole Christian Lingjærde, David C. Wedge, Peter Van Loo, on behalf of the PCAWG Evolution and Heterogeneity Working Group, Stefan C. Dentro, Ignaty Leshchiner, Moritz Gerstung, Clemency Jolly, Kerstin Haase, Jeff Wintersinger, Pavana Anur, Rameen Beroukhim, Paul C. Boutros, David D. Bowtell, Peter J. Campbell, Elizabeth L. Christie, Marek Cmero, Yupeng Cun, Kevin Dawson, Jonas Demeulemeester, Amit Deshwar, Nilgun Donmez, Roland Eils, Yu Fan, Matthew Fittall, Dale W. Garsed, Gad Getz, Santiago Gonzalez, Gavin Ha, Marcin Imielinski, Yuan Ji, Kortine Kleinheinz, Juhee Lee, Henry Lee-Six, Dimitri G. Livitz, Geoff Macintyre, Salem Malikic, Florian Markowetz, Inigo Martincorena, Thomas J. Mitchell, Ville Mustonen, Layla Oesper, Martin Peifer, Myron Peto, Benjamin J. Raphael, Daniel Rosebrock, Yulia Rubanova, S. Cenk Sahinalp, Adriana Salcedo, Matthias Schlesner, Steve Schumacher, Subhajit Sengupta, Lincoln D. Stein, Maxime Tarabichi, Ignacio Vázquez-García, Shankar Vembu, Wenyi Wang, David A. Wheeler, Tsun-Po Yang, Xiaotong Yao, Fouad Yousif, Kaixian Yu, Ke Yuan, Hongtu Zhu, Quaid D. Morris, Paul T. Spellman, David C. Wedge, Peter Van Loo
doi: https://doi.org/10.1101/158006
Maxime Tarabichi
The Francis Crick Institute, London, United Kingdom;
Iñigo Martincorena
Wellcome Trust Sanger Institute, Cambridge, United Kingdom;
Moritz Gerstung
European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Cambridge, United Kingdom;
Florian Markowetz
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom;
Paul T. Spellman
Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA;
Quaid D. Morris
University of Toronto, Toronto, Canada;
Ole Christian Lingjærde
Department of Informatics and Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway;
David C. Wedge
Big Data Institute, University of Oxford, Oxford, United Kingdom;
Peter Van Loo
The Francis Crick Institute, London, United Kingdom;Department of Human Genetics, University of Leuven, Leuven, Belgium;
PCAWG Evolution and Heterogeneity Working Group
Stefan C. Dentro
The Francis Crick Institute, London NW1 1AT, United Kingdom;Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;Big Data Institute, University of Oxford, Oxford OX3 7BN, United Kingdom;
Ignaty Leshchiner
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Moritz Gerstung
European Bioinformatics Ititute (EMBL-EBI), European Molecular Biology Laboratory, Cambridge CB10 1SD, United Kingdom;
Clemency Jolly
The Francis Crick Institute, London NW1 1AT, United Kingdom;
Kerstin Haase
The Francis Crick Institute, London NW1 1AT, United Kingdom;
Jeff Wintersinger
University of Toronto, Toronto, ON M5S 3E1, Canada;
Pavana Anur
Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA;
Rameen Beroukhim
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Paul C. Boutros
University of Toronto, Toronto, ON M5S 3E1, Canada;Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
David D. Bowtell
Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia;Garvan Institute of Medical Research, Sydney, NSW 2010, Australia;
Peter J. Campbell
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Elizabeth L. Christie
Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia;
Marek Cmero
University of Melbourne, Melbourne, VIC 3010, Australia;
Yupeng Cun
University of Cologne, 50931 Cologne, Germany;
Kevin Dawson
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Jonas Demeulemeester
The Francis Crick Institute, London NW1 1AT, United Kingdom;Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium;
Amit Deshwar
University of Toronto, Toronto, ON M5S 3E1, Canada;
Nilgun Donmez
Simon Fraser University, Burnaby, BC V5A1S6, Canada;
Roland Eils
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;Heidelberg University, 69120 Heidelberg, Germany;
Yu Fan
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
Matthew Fittall
The Francis Crick Institute, London NW1 1AT, United Kingdom;
Dale W. Garsed
Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia;
Gad Getz
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Santiago Gonzalez
European Bioinformatics Ititute (EMBL-EBI), European Molecular Biology Laboratory, Cambridge CB10 1SD, United Kingdom;
Gavin Ha
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Marcin Imielinski
Weill Cornell Medicine, New York, NY 10065, USA;New York Genome Center, New York, NY 10013, USA;
Yuan Ji
NorthShore University HealthSystem, Evanston, IL 60201, USA;The University of Chicago, Chicago, IL 60637, USA;
Kortine Kleinheinz
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;Heidelberg University, 69120 Heidelberg, Germany;
Juhee Lee
University of California Santa Cruz, Santa Cruz, CA 95064, USA;
Henry Lee-Six
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Dimitri G. Livitz
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Geoff Macintyre
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom;
Salem Malikic
Simon Fraser University, Burnaby, BC V5A1S6, Canada;
Florian Markowetz
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom;
Inigo Martincorena
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Thomas J. Mitchell
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
Ville Mustonen
University of Helsinki, 00014 Helsinki, Finland;
Layla Oesper
Carleton College, Northfield, MN 55057, USA;
Martin Peifer
University of Cologne, 50931 Cologne, Germany;
Myron Peto
Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA;
Benjamin J. Raphael
Princeton University, Princeton, NJ 08540, USA;
Daniel Rosebrock
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Yulia Rubanova
University of Toronto, Toronto, ON M5S 3E1, Canada;
S. Cenk Sahinalp
Indiana University, Bloomington, IN 47405, USA;
Adriana Salcedo
Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
Matthias Schlesner
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
Steve Schumacher
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Subhajit Sengupta
NorthShore University HealthSystem, Evanston, IL 60201, USA;
Lincoln D. Stein
Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
Maxime Tarabichi
The Francis Crick Institute, London NW1 1AT, United Kingdom;
Ignacio Vázquez-García
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
Shankar Vembu
University of Toronto, Toronto, ON M5S 3E1, Canada;
Wenyi Wang
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
David A. Wheeler
Baylor College of Medicine, Houston, TX 77030, USA;
Tsun-Po Yang
University of Cologne, 50931 Cologne, Germany;
Xiaotong Yao
Weill Cornell Medicine, New York, NY 10065, USA;New York Genome Center, New York, NY 10013, USA;
Fouad Yousif
Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
Kaixian Yu
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
Ke Yuan
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom;University of Glasgow, Glasgow G12 8RZ, United Kingdom.
Hongtu Zhu
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
Quaid D. Morris
University of Toronto, Toronto, ON M5S 3E1, Canada;
Paul T. Spellman
Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA;
David C. Wedge
Big Data Institute, University of Oxford, Oxford OX3 7BN, United Kingdom;
Peter Van Loo
The Francis Crick Institute, London NW1 1AT, United Kingdom;Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium;
Abstract
Williams et al. (Nat. Genet. 48:238-224, 2016) recently reported neutral tumor evolution in one third of 904 samples from The Cancer Genome Atlas. Here, we assess the reproducibility and validity of their method and the extent of positive selection in subclonal mutations across cancer types. Our results do not support observable neutral tumor evolution and uncover strong positive selection within subclonal mutations across cancers.
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-NC-ND 4.0 International license.
Posted June 30, 2017.
Neutral tumor evolution?
Maxime Tarabichi, Iñigo Martincorena, Moritz Gerstung, Florian Markowetz, Paul T. Spellman, Quaid D. Morris, Ole Christian Lingjærde, David C. Wedge, Peter Van Loo, on behalf of the PCAWG Evolution and Heterogeneity Working Group, Stefan C. Dentro, Ignaty Leshchiner, Moritz Gerstung, Clemency Jolly, Kerstin Haase, Jeff Wintersinger, Pavana Anur, Rameen Beroukhim, Paul C. Boutros, David D. Bowtell, Peter J. Campbell, Elizabeth L. Christie, Marek Cmero, Yupeng Cun, Kevin Dawson, Jonas Demeulemeester, Amit Deshwar, Nilgun Donmez, Roland Eils, Yu Fan, Matthew Fittall, Dale W. Garsed, Gad Getz, Santiago Gonzalez, Gavin Ha, Marcin Imielinski, Yuan Ji, Kortine Kleinheinz, Juhee Lee, Henry Lee-Six, Dimitri G. Livitz, Geoff Macintyre, Salem Malikic, Florian Markowetz, Inigo Martincorena, Thomas J. Mitchell, Ville Mustonen, Layla Oesper, Martin Peifer, Myron Peto, Benjamin J. Raphael, Daniel Rosebrock, Yulia Rubanova, S. Cenk Sahinalp, Adriana Salcedo, Matthias Schlesner, Steve Schumacher, Subhajit Sengupta, Lincoln D. Stein, Maxime Tarabichi, Ignacio Vázquez-García, Shankar Vembu, Wenyi Wang, David A. Wheeler, Tsun-Po Yang, Xiaotong Yao, Fouad Yousif, Kaixian Yu, Ke Yuan, Hongtu Zhu, Quaid D. Morris, Paul T. Spellman, David C. Wedge, Peter Van Loo
bioRxiv 158006; doi: https://doi.org/10.1101/158006
Neutral tumor evolution?
Maxime Tarabichi, Iñigo Martincorena, Moritz Gerstung, Florian Markowetz, Paul T. Spellman, Quaid D. Morris, Ole Christian Lingjærde, David C. Wedge, Peter Van Loo, on behalf of the PCAWG Evolution and Heterogeneity Working Group, Stefan C. Dentro, Ignaty Leshchiner, Moritz Gerstung, Clemency Jolly, Kerstin Haase, Jeff Wintersinger, Pavana Anur, Rameen Beroukhim, Paul C. Boutros, David D. Bowtell, Peter J. Campbell, Elizabeth L. Christie, Marek Cmero, Yupeng Cun, Kevin Dawson, Jonas Demeulemeester, Amit Deshwar, Nilgun Donmez, Roland Eils, Yu Fan, Matthew Fittall, Dale W. Garsed, Gad Getz, Santiago Gonzalez, Gavin Ha, Marcin Imielinski, Yuan Ji, Kortine Kleinheinz, Juhee Lee, Henry Lee-Six, Dimitri G. Livitz, Geoff Macintyre, Salem Malikic, Florian Markowetz, Inigo Martincorena, Thomas J. Mitchell, Ville Mustonen, Layla Oesper, Martin Peifer, Myron Peto, Benjamin J. Raphael, Daniel Rosebrock, Yulia Rubanova, S. Cenk Sahinalp, Adriana Salcedo, Matthias Schlesner, Steve Schumacher, Subhajit Sengupta, Lincoln D. Stein, Maxime Tarabichi, Ignacio Vázquez-García, Shankar Vembu, Wenyi Wang, David A. Wheeler, Tsun-Po Yang, Xiaotong Yao, Fouad Yousif, Kaixian Yu, Ke Yuan, Hongtu Zhu, Quaid D. Morris, Paul T. Spellman, David C. Wedge, Peter Van Loo
bioRxiv 158006; doi: https://doi.org/10.1101/158006
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