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
1The Francis Crick Institute, London, United Kingdom;
Iñigo Martincorena
2Wellcome Trust Sanger Institute, Cambridge, United Kingdom;
Moritz Gerstung
3European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Cambridge, United Kingdom;
Florian Markowetz
4Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom;
Paul T. Spellman
5Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA;
Quaid D. Morris
6University of Toronto, Toronto, Canada;
Ole Christian Lingjærde
7Department of Informatics and Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway;
David C. Wedge
8Big Data Institute, University of Oxford, Oxford, United Kingdom;
Peter Van Loo
1The Francis Crick Institute, London, United Kingdom;
9Department of Human Genetics, University of Leuven, Leuven, Belgium;
10PCAWG Evolution and Heterogeneity Working Group
Stefan C. Dentro
1The Francis Crick Institute, London NW1 1AT, United Kingdom;
2Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
3Big Data Institute, University of Oxford, Oxford OX3 7BN, United Kingdom;
Ignaty Leshchiner
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Moritz Gerstung
5European Bioinformatics Ititute (EMBL-EBI), European Molecular Biology Laboratory, Cambridge CB10 1SD, United Kingdom;
Clemency Jolly
1The Francis Crick Institute, London NW1 1AT, United Kingdom;
Kerstin Haase
1The Francis Crick Institute, London NW1 1AT, United Kingdom;
Jeff Wintersinger
6University of Toronto, Toronto, ON M5S 3E1, Canada;
Pavana Anur
7Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA;
Rameen Beroukhim
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Paul C. Boutros
6University of Toronto, Toronto, ON M5S 3E1, Canada;
8Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
David D. Bowtell
9Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia;
10Garvan Institute of Medical Research, Sydney, NSW 2010, Australia;
Peter J. Campbell
2Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Elizabeth L. Christie
9Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia;
Marek Cmero
11University of Melbourne, Melbourne, VIC 3010, Australia;
Yupeng Cun
12University of Cologne, 50931 Cologne, Germany;
Kevin Dawson
2Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Jonas Demeulemeester
1The Francis Crick Institute, London NW1 1AT, United Kingdom;
13Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium;
Amit Deshwar
6University of Toronto, Toronto, ON M5S 3E1, Canada;
Nilgun Donmez
14Simon Fraser University, Burnaby, BC V5A1S6, Canada;
Roland Eils
15German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
16Heidelberg University, 69120 Heidelberg, Germany;
Yu Fan
17The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
Matthew Fittall
1The Francis Crick Institute, London NW1 1AT, United Kingdom;
Dale W. Garsed
9Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia;
Gad Getz
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Santiago Gonzalez
5European Bioinformatics Ititute (EMBL-EBI), European Molecular Biology Laboratory, Cambridge CB10 1SD, United Kingdom;
Gavin Ha
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Marcin Imielinski
18Weill Cornell Medicine, New York, NY 10065, USA;
19New York Genome Center, New York, NY 10013, USA;
Yuan Ji
20NorthShore University HealthSystem, Evanston, IL 60201, USA;
21The University of Chicago, Chicago, IL 60637, USA;
Kortine Kleinheinz
15German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
16Heidelberg University, 69120 Heidelberg, Germany;
Juhee Lee
22University of California Santa Cruz, Santa Cruz, CA 95064, USA;
Henry Lee-Six
2Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Dimitri G. Livitz
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Geoff Macintyre
23Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom;
Salem Malikic
14Simon Fraser University, Burnaby, BC V5A1S6, Canada;
Florian Markowetz
23Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom;
Inigo Martincorena
2Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
Thomas J. Mitchell
2Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
24University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
Ville Mustonen
25University of Helsinki, 00014 Helsinki, Finland;
Layla Oesper
26Carleton College, Northfield, MN 55057, USA;
Martin Peifer
12University of Cologne, 50931 Cologne, Germany;
Myron Peto
7Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA;
Benjamin J. Raphael
27Princeton University, Princeton, NJ 08540, USA;
Daniel Rosebrock
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Yulia Rubanova
6University of Toronto, Toronto, ON M5S 3E1, Canada;
S. Cenk Sahinalp
28Indiana University, Bloomington, IN 47405, USA;
Adriana Salcedo
8Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
Matthias Schlesner
15German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
Steve Schumacher
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;
Subhajit Sengupta
20NorthShore University HealthSystem, Evanston, IL 60201, USA;
Lincoln D. Stein
8Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
Maxime Tarabichi
1The Francis Crick Institute, London NW1 1AT, United Kingdom;
Ignacio Vázquez-García
2Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
24University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
Shankar Vembu
6University of Toronto, Toronto, ON M5S 3E1, Canada;
Wenyi Wang
17The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
David A. Wheeler
29Baylor College of Medicine, Houston, TX 77030, USA;
Tsun-Po Yang
12University of Cologne, 50931 Cologne, Germany;
Xiaotong Yao
18Weill Cornell Medicine, New York, NY 10065, USA;
19New York Genome Center, New York, NY 10013, USA;
Fouad Yousif
8Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada;
Kaixian Yu
17The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
Ke Yuan
23Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom;
30University of Glasgow, Glasgow G12 8RZ, United Kingdom.
Hongtu Zhu
17The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
Quaid D. Morris
6University of Toronto, Toronto, ON M5S 3E1, Canada;
Paul T. Spellman
7Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA;
David C. Wedge
3Big Data Institute, University of Oxford, Oxford OX3 7BN, United Kingdom;
Peter Van Loo
1The Francis Crick Institute, London NW1 1AT, United Kingdom;
13Department 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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