title: Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer.
abstract: Human colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, to what extent these established cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 colorectal cancer cell lines for mutations and DNA copy number by whole-exome sequencing and SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published for primary colorectal cancers in The Cancer Genome Atlas. Notably, we found that exome mutation and DNA copy-number spectra in colorectal cancer cell lines closely resembled those seen in primary colorectal tumors. Similarities included the presence of two hypermutation phenotypes, as defined by signatures for defective DNA mismatch repair and DNA polymerase ε proofreading deficiency, along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGFβ, and p53 pathways. Furthermore, we documented mutations enriched in genes involved in chromatin remodeling (ARID1A, CHD6, and SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, and TRRAP). Chromosomal instability was prevalent in nonhypermutated cases, with similar patterns of chromosomal gains and losses. Although paired cell lines derived from the same tumor exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differences mainly reflected a preexisting heterogeneity in the tumor cells. In conclusion, our results establish that human colorectal cancer lines are representative of the main subtypes of primary tumors at the genomic level, further validating their utility as tools to investigate colorectal cancer biology and drug responses.
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Dmitri
authors.initials: D
authors.lastname: Mouradov
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Sloggett
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Robert N
authors.initials: RN
authors.lastname: Jorissen
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Love
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Antony W
authors.initials: AW
authors.lastname: Burgess
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Diego
authors.initials: D
authors.lastname: Arango
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Robert L
authors.initials: RL
authors.lastname: Strausberg
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Buchanan
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Samuel
authors.initials: S
authors.lastname: Wormald
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Liam
authors.initials: L
authors.lastname: O'Connor
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wilding
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Bicknell
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Ian P M
authors.initials: IP
authors.lastname: Tomlinson
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Walter F
authors.initials: WF
authors.lastname: Bodmer
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom John.Mariadason@ludwig.edu.au Oliver.Sieber@wehi.edu.au.
authors.forename: John M
authors.initials: JM
authors.lastname: Mariadason
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies Group, Queensland Institute of Medical Research, Herston, QLD, Australia; Group of Molecular Oncology, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN); Spain; Ludwig Collaborative Laboratory for Cancer Biology and Therapy, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Institute for Cancer Research Ltd., New York, New York; Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford; and Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomAuthors' Affiliations: Ludwig Institute for Cancer Research; Systems Biology and Personalised Medicine Division; Structural Biology Division; Walter and Eliza Hall Institute of Medical Research; Faculty of Medicine, Dentistry and Health Sciences, Department of Medical Biology, University of Melbourne, Parkville; VLSCI Life Sciences Computation Centre, a collaboration between Melbourne, Monash and LaTrobe Universities, c/o The University of Melbourne, Carlton; Oncogenic Transcription Laboratory, Ludwig Institute for Cancer Research, Austin, VIC, Australia; Cancer and Population Studies 
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Sieber
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D059472:Exome; D018628:Gene Dosage; D005787:Gene Frequency; D052138:Genes, Neoplasm; D006801:Humans; D053842:Microsatellite Instability; D059467:Transcriptome