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      The evolutionary history of 2,658 cancers

      research-article
      1 , 2 , 3 , , 4 , 5 , 3 , 4 , 6 , 1 , 5 , 3 , 7 , 8 , 9 , 10 , 11 , 3 , 4 , 8 , 9 , 8 , 9 , 12 , 13 , 3 , 7 , 4 , 1 , 14 , 15 , 16 , 17 , 18 , 17 , 18 , 5 , 19 , 20 , 4 , 21 , 5 , 11 , 22 , 23 , 24 , 12 , 8 , 25 , 26 , 27 , 11 , 5 , 28 , 29 , 30 , 22 , 23 , 5 , 31 , 18 , 32 , 15 , 33 , 34 , 16 , 35 , 16 , 36 , 11 , 8 , 9 , PCAWG Evolution & Heterogeneity Working Group, 10 , 6 , 38 , 4 , 21 , , PCAWG Consortium
      Nature
      Nature Publishing Group UK
      Cancer genomics, Computational biology and bioinformatics, Molecular evolution, Cancer genomics

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          Abstract

          Cancer develops through a process of somatic evolution 1, 2 . Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes 3 . Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) 4 , we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.

          Abstract

          Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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          Most cited references18

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          A genetic model for colorectal tumorigenesis.

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            • Record: found
            • Abstract: found
            • Article: not found

            The clonal evolution of tumor cell populations.

            P C Nowell (1976)
            It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
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              • Record: found
              • Abstract: not found
              • Article: not found

              Mutation selection and the natural history of cancer.

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                Author and article information

                Contributors
                moritz.gerstung@ebi.ac.uk
                peter.vanloo@crick.ac.uk
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                5 February 2020
                5 February 2020
                2020
                : 578
                : 7793
                : 122-128
                Affiliations
                [1 ]ISNI 0000 0000 9709 7726, GRID grid.225360.0, European Molecular Biology Laboratory, , European Bioinformatics Institute (EMBL-EBI), ; Cambridge, UK
                [2 ]ISNI 0000 0004 0495 846X, GRID grid.4709.a, European Molecular Biology Laboratory, , Genome Biology Unit, ; Heidelberg, Germany
                [3 ]ISNI 0000 0004 0606 5382, GRID grid.10306.34, Wellcome Sanger Institute, ; Cambridge, UK
                [4 ]ISNI 0000 0004 1795 1830, GRID grid.451388.3, The Francis Crick Institute, ; London, UK
                [5 ]GRID grid.66859.34, Broad Institute of MIT and Harvard, ; Cambridge, MA USA
                [6 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Big Data Institute, , University of Oxford, ; Oxford, UK
                [7 ]ISNI 0000000121885934, GRID grid.5335.0, University of Cambridge, ; Cambridge, UK
                [8 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, University of Toronto, ; Toronto, Ontario Canada
                [9 ]GRID grid.494618.6, Vector Institute, ; Toronto, Ontario Canada
                [10 ]ISNI 0000 0000 9758 5690, GRID grid.5288.7, Molecular and Medical Genetics, , Oregon Health & Science University, ; Portland, OR USA
                [11 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, The University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [12 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, German Cancer Research Center (DKFZ), ; Heidelberg, Germany
                [13 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Heidelberg University, ; Heidelberg, Germany
                [14 ]ISNI 0000 0001 0721 6013, GRID grid.8954.0, University of Ljubljana, ; Ljubljana, Slovenia
                [15 ]ISNI 0000 0004 0400 4439, GRID grid.240372.0, NorthShore University HealthSystem, ; Evanston, IL USA
                [16 ]ISNI 0000000121885934, GRID grid.5335.0, Cancer Research UK Cambridge Institute, , University of Cambridge, ; Cambridge, UK
                [17 ]ISNI 0000 0004 1936 7494, GRID grid.61971.38, Simon Fraser University, ; Burnaby, British Columbia Canada
                [18 ]ISNI 0000 0001 0684 7796, GRID grid.412541.7, Vancouver Prostate Centre, ; Vancouver, British Columbia Canada
                [19 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, University of Melbourne, ; Melbourne, Victoria Australia
                [20 ]GRID grid.1042.7, Walter and Eliza Hall Institute, ; Melbourne, Victoria Australia
                [21 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, University of Leuven, ; Leuven, Belgium
                [22 ]ISNI 000000041936877X, GRID grid.5386.8, Weill Cornell Medicine, ; New York, NY USA
                [23 ]GRID grid.429884.b, New York Genome Center, ; New York, NY USA
                [24 ]ISNI 0000 0001 0740 6917, GRID grid.205975.c, University of California Santa Cruz, ; Santa Cruz, CA USA
                [25 ]ISNI 0000 0004 0626 690X, GRID grid.419890.d, Ontario Institute for Cancer Research, ; Toronto, Ontario Canada
                [26 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, University of California, ; Los Angeles, CA USA
                [27 ]ISNI 0000000403978434, GRID grid.1055.1, Peter MacCallum Cancer Centre, ; Melbourne, Victoria Australia
                [28 ]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Center for Cancer Research, , Massachusetts General Hospital, ; Charlestown, MA USA
                [29 ]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Department of Pathology, , Massachusetts General Hospital, ; Boston, MA USA
                [30 ]ISNI 000000041936754X, GRID grid.38142.3c, Harvard Medical School, ; Boston, MA USA
                [31 ]ISNI 0000 0001 2106 9910, GRID grid.65499.37, Dana-Farber Cancer Institute, ; Boston, MA USA
                [32 ]ISNI 0000 0001 0790 959X, GRID grid.411377.7, Indiana University, ; Bloomington, IN USA
                [33 ]ISNI 0000 0004 1936 7822, GRID grid.170205.1, The University of Chicago, ; Chicago, IL USA
                [34 ]ISNI 0000 0000 8580 3777, GRID grid.6190.e, University of Cologne, ; Cologne, Germany
                [35 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, University of Helsinki, ; Helsinki, Finland
                [36 ]ISNI 0000 0001 2193 314X, GRID grid.8756.c, University of Glasgow, ; Glasgow, UK
                [38 ]GRID grid.454382.c, Oxford NIHR Biomedical Research Centre, ; Oxford, UK
                [42 ]ISNI 0000 0004 0445 5969, GRID grid.253692.9, Department of Computer Science, , Carleton College, ; Northfield, MN USA
                [43 ]ISNI 0000 0001 2097 5006, GRID grid.16750.35, Department of Computer Science, , Princeton University, ; Princeton, NJ USA
                [44 ]ISNI 0000 0001 0840 2678, GRID grid.222754.4, Korea University, ; Seoul, South Korea
                [45 ]ISNI 0000 0001 2160 926X, GRID grid.39382.33, Human Genome Sequencing Center, , Baylor College of Medicine, ; Houston, TX USA
                Article
                1907
                10.1038/s41586-019-1907-7
                7054212
                32025013
                32ef89c9-2adc-48ad-8fa7-8ee3cc7af17c
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 August 2017
                : 18 November 2019
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                © The Author(s), under exclusive licence to Springer Nature Limited 2020

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                cancer genomics,computational biology and bioinformatics,molecular evolution
                Uncategorized
                cancer genomics, computational biology and bioinformatics, molecular evolution

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