A RENEWED MODEL OF PANCREAS CANCER EVOLUTION BASED ON GENOMIC REARRANGEMENT PATTERNS
Pancreas cancer (PC), a highly aggressive tumour type with uniformly poor prognosis, is an exemplar of the classical view of cancer development based on stepwise progression 1 . The current progression model, based on analyses of precursor lesions termed pancreatic intraepithelial neoplasm (PanINs)...
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| Published in | Nature (London) Vol. 538; no. 7625; pp. 378 - 382 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
12.10.2016
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| Online Access | Get full text |
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| Abstract | Pancreas cancer (PC), a highly aggressive tumour type with uniformly poor prognosis, is an exemplar of the classical view of cancer development based on stepwise progression
1
. The current progression model, based on analyses of precursor lesions termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: 1) PC develops through a particular sequence of genetic alterations
2
–
5
(
KRAS
>
CDKN2A
>
TP53/SMAD4
); and 2) the evolutionary trajectory of PC progression is gradual because each alteration is acquired independently. One shortcoming of this nearly two decade old contention is that clonally expanded precursor lesions have been identified that do not always belong to the tumour lineage
2
,
5
–
9
, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing view of tumourigenesis has contributed to the clinical notion that PC evolves slowly and presents at a late stage
10
. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes despite efforts aimed at early detection
11
, argue that PC progression is anything but gradual. By tracking DNA copy number changes and their associated rearrangements from tumour-enriched genomes using novel informatics tools, we found that PC tumourigenesis neither is gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory
12
. In a subset of cases, the consequence of such errors was the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that likely set-off invasive cancer growth. These findings challenge the current model of PC tumourigenesis and provide novel insights into the mutational processes giving rise to these aggressive tumours. |
|---|---|
| AbstractList | Pancreas cancer (PC), a highly aggressive tumour type with uniformly poor prognosis, is an exemplar of the classical view of cancer development based on stepwise progression
1
. The current progression model, based on analyses of precursor lesions termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: 1) PC develops through a particular sequence of genetic alterations
2
–
5
(
KRAS
>
CDKN2A
>
TP53/SMAD4
); and 2) the evolutionary trajectory of PC progression is gradual because each alteration is acquired independently. One shortcoming of this nearly two decade old contention is that clonally expanded precursor lesions have been identified that do not always belong to the tumour lineage
2
,
5
–
9
, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing view of tumourigenesis has contributed to the clinical notion that PC evolves slowly and presents at a late stage
10
. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes despite efforts aimed at early detection
11
, argue that PC progression is anything but gradual. By tracking DNA copy number changes and their associated rearrangements from tumour-enriched genomes using novel informatics tools, we found that PC tumourigenesis neither is gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory
12
. In a subset of cases, the consequence of such errors was the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that likely set-off invasive cancer growth. These findings challenge the current model of PC tumourigenesis and provide novel insights into the mutational processes giving rise to these aggressive tumours. |
| Author | Law, Calvin Wilson, Gavin W Wilson, Julie M Lemire, Mathieu Wang, Tao Li, Yilong Shlush, Liran I Real, Francisco X Heisler, Lawrence Timms, Lee Lungu, Ilinca Roehrl, Michael H Brown, Andrew MK Yung, Christina K Hafezi-Bakhtiari, Sara Campbell, Peter J Ng, Karen Cleary, Sean P Gallinger, Steven Beck, Timothy Tsao, Ming-Sound Stein, Lincoln D Hudson, Thomas J Chan-Seng-Yue, Michelle Dick, John E Jorgensen, Lars GT Connor, Ashton A Borgida, Ayelet Ludkovski, Olga Pasternack, Danielle Simpson, Jared T Kim, Jaeseung C Notta, Faiyaz Denroche, Rob E Ibrahimov, Emin Zogopoulos, George Hollingsworth, Michael A Petersen, Gloria M Jang, Gun Ho Johns, Jeremy Liang, Sheng-Ben McPherson, John D Chadwick, Dianne Bartlett, John MS Alexandrov, Ludmil B Buchner, Nicholas |
| AuthorAffiliation | 3 UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada 5 Molecular Genetics, University of Toronto, Toronto, ON, Canada 16 Department of Surgery, University Health Network, Toronto, Ontario, Canada 12 Research Institute of the McGill University Health Centre, Montreal, QC, Canada 1 Ontario Institute for Cancer Research, Toronto, Ontario Canada 4 Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada 11 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA 6 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 2 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK 8 Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada 17 Department of Hematology, University of Cambridge, Cambridge, UK 7 Department of Computer Science, University of Toronto, Toronto, Ontario, Canada 14 Epithelial Carcinogenesis Group, Spanish National Cancer Resea |
| AuthorAffiliation_xml | – name: 4 Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada – name: 13 Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA – name: 2 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK – name: 3 UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada – name: 17 Department of Hematology, University of Cambridge, Cambridge, UK – name: 10 Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada – name: 8 Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada – name: 15 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada – name: 11 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA – name: 14 Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain – name: 1 Ontario Institute for Cancer Research, Toronto, Ontario Canada – name: 7 Department of Computer Science, University of Toronto, Toronto, Ontario, Canada – name: 12 Research Institute of the McGill University Health Centre, Montreal, QC, Canada – name: 5 Molecular Genetics, University of Toronto, Toronto, ON, Canada – name: 6 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada – name: 16 Department of Surgery, University Health Network, Toronto, Ontario, Canada – name: 9 Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA |
| Author_xml | – sequence: 1 givenname: Faiyaz surname: Notta fullname: Notta, Faiyaz organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 2 givenname: Michelle surname: Chan-Seng-Yue fullname: Chan-Seng-Yue, Michelle organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 3 givenname: Mathieu surname: Lemire fullname: Lemire, Mathieu organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 4 givenname: Yilong surname: Li fullname: Li, Yilong organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 5 givenname: Gavin W surname: Wilson fullname: Wilson, Gavin W organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 6 givenname: Ashton A surname: Connor fullname: Connor, Ashton A organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 7 givenname: Rob E surname: Denroche fullname: Denroche, Rob E organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 8 givenname: Sheng-Ben surname: Liang fullname: Liang, Sheng-Ben organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 9 givenname: Andrew MK surname: Brown fullname: Brown, Andrew MK organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 10 givenname: Jaeseung C surname: Kim fullname: Kim, Jaeseung C organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 11 givenname: Tao surname: Wang fullname: Wang, Tao organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 12 givenname: Jared T surname: Simpson fullname: Simpson, Jared T organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 13 givenname: Timothy surname: Beck fullname: Beck, Timothy organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 14 givenname: Ayelet surname: Borgida fullname: Borgida, Ayelet organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 15 givenname: Nicholas surname: Buchner fullname: Buchner, Nicholas organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 16 givenname: Dianne surname: Chadwick fullname: Chadwick, Dianne organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 17 givenname: Sara surname: Hafezi-Bakhtiari fullname: Hafezi-Bakhtiari, Sara organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 18 givenname: John E surname: Dick fullname: Dick, John E organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 19 givenname: Lawrence surname: Heisler fullname: Heisler, Lawrence organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 20 givenname: Michael A surname: Hollingsworth fullname: Hollingsworth, Michael A organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 21 givenname: Emin surname: Ibrahimov fullname: Ibrahimov, Emin organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 22 givenname: Gun Ho surname: Jang fullname: Jang, Gun Ho organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 23 givenname: Jeremy surname: Johns fullname: Johns, Jeremy organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 24 givenname: Lars GT surname: Jorgensen fullname: Jorgensen, Lars GT organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 25 givenname: Calvin surname: Law fullname: Law, Calvin organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 26 givenname: Olga surname: Ludkovski fullname: Ludkovski, Olga organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 27 givenname: Ilinca surname: Lungu fullname: Lungu, Ilinca organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 28 givenname: Karen surname: Ng fullname: Ng, Karen organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 29 givenname: Danielle surname: Pasternack fullname: Pasternack, Danielle organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 30 givenname: Gloria M surname: Petersen fullname: Petersen, Gloria M organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 31 givenname: Liran I surname: Shlush fullname: Shlush, Liran I organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 32 givenname: Lee surname: Timms fullname: Timms, Lee organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 33 givenname: Ming-Sound surname: Tsao fullname: Tsao, Ming-Sound organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 34 givenname: Julie M surname: Wilson fullname: Wilson, Julie M organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 35 givenname: Christina K surname: Yung fullname: Yung, Christina K organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 36 givenname: George surname: Zogopoulos fullname: Zogopoulos, George organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 37 givenname: John MS surname: Bartlett fullname: Bartlett, John MS organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 38 givenname: Ludmil B surname: Alexandrov fullname: Alexandrov, Ludmil B organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 39 givenname: Francisco X surname: Real fullname: Real, Francisco X organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 40 givenname: Sean P surname: Cleary fullname: Cleary, Sean P organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 41 givenname: Michael H surname: Roehrl fullname: Roehrl, Michael H organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 42 givenname: John D surname: McPherson fullname: McPherson, John D organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 43 givenname: Lincoln D surname: Stein fullname: Stein, Lincoln D organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 44 givenname: Thomas J surname: Hudson fullname: Hudson, Thomas J organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 45 givenname: Peter J surname: Campbell fullname: Campbell, Peter J organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK – sequence: 46 givenname: Steven surname: Gallinger fullname: Gallinger, Steven organization: Ontario Institute for Cancer Research, Toronto, Ontario Canada Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK UHN Program in BioSpecimen Sciences, Department of Pathology, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Department of Computer Science, University of Toronto, Toronto, Ontario, Canada Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada Eppley Institute for Research in Cancer, Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Research Institute of the McGill University Health Centre, Montreal, QC, Canada Theoretical Biology and Biophysics (T-6) and Center for Nonlinear Studies, Los Alamos National Laboratory,Los Alamos, New Mexico, USA Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada Department of Surgery, University Health Network, Toronto, Ontario, Canada Department of Hematology, University of Cambridge, Cambridge, UK |
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| Snippet | Pancreas cancer (PC), a highly aggressive tumour type with uniformly poor prognosis, is an exemplar of the classical view of cancer development based on... |
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| Title | A RENEWED MODEL OF PANCREAS CANCER EVOLUTION BASED ON GENOMIC REARRANGEMENT PATTERNS |
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