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Nature. 2015 Apr 16;520(7547):353-357. doi: 10.1038/nature14347 Q148.52025

The evolutionary history of lethal metastatic prostate cancer

致命性转移性前列腺癌的进化历史 翻译改进

Gunes Gundem  1, Peter Van Loo  1  2  3, Barbara Kremeyer  1, Ludmil B Alexandrov  1, Jose M C Tubio  1, Elli Papaemmanuil  1, Daniel S Brewer  4, Heini M L Kallio  5, Gunilla Högnäs  5, Matti Annala  5, Kati Kivinummi  5, Victoria Goody  1, Calli Latimer  1, Sarah O'Meara  1, Kevin J Dawson  1, William Isaacs  6, Michael R Emmert-Buck  7, Matti Nykter  5, Christopher Foster  8  9, Zsofia Kote-Jarai  10, Douglas Easton  11  9, Hayley C Whitaker  12; ICGC Prostate Group; David E Neal  12  13  9, Colin S Cooper  10  4  9, Rosalind A Eeles  10  14  9, Tapio Visakorpi  5, Peter J Campbell  1, Ultan McDermott  1  9, David C Wedge  1, G Steven Bova  5  9

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作者单位

  • 1 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
  • 2 Department of Human Genetics, KU Leuven, Herestraat 49 Box 602, B-3000 Leuven, Belgium.
  • 3 Cancer Research UK London Research Institute, London, UK.
  • 4 Norwich Medical School and Department of Biological Sciences, University of East Anglia, Norwich, UK.
  • 5 Institute of Biosciences and Medical Technology, BioMediTech, University of Tampere and Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
  • 6 The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • 7 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, MD, USA.
  • 8 University of Liverpool and HCA Pathology Laboratories, London, UK.
  • 9 Senior Principal Investigators of the Cancer Research UK funded ICGC Prostate Cancer Project.
  • 10 Division of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
  • 11 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • 12 Uro-oncology Research Group, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
  • 13 Department of Surgical Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
  • 14 Royal Marsden NHS Foundation Trust, London and Sutton, UK.
  • DOI: 10.1038/nature14347 PMID: 25830880

    摘要 Ai翻译

    Cancers emerge from an ongoing Darwinian evolutionary process, often leading to multiple competing subclones within a single primary tumour. This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths. However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported, recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and interclonal cooperation between multiple subclones. Here we sought definitive evidence for the existence of polyclonal seeding in human malignancy and to establish the clonal relationship among different metastases in the context of androgen-deprived metastatic prostate cancer. Using whole-genome sequencing, we characterized multiple metastases arising from prostate tumours in ten patients. Integrated analyses of subclonal architecture revealed the patterns of metastatic spread in unprecedented detail. Metastasis-to-metastasis spread was found to be common, either through de novo monoclonal seeding of daughter metastases or, in five cases, through the transfer of multiple tumour clones between metastatic sites. Lesions affecting tumour suppressor genes usually occur as single events, whereas mutations in genes involved in androgen receptor signalling commonly involve multiple, convergent events in different metastases. Our results elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer.

    Keywords:evolutionary history; metastatic prostate cancer

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    期刊名:Nature

    缩写:NATURE

    ISSN:0028-0836

    e-ISSN:1476-4687

    IF/分区:48.5/Q1

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