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Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy

  1. Author:
    Woodcock, D J [ORCID]
    Riabchenko, E
    Taavitsainen, S
    Kankainen, M [ORCID]
    Gundem, G [ORCID]
    Brewer, D S [ORCID]
    Ellonen, P
    Lepistö, M
    Golubeva, Y A
    Warner,Andrew [ORCID]
    Tolonen, T
    Jasu, J [ORCID]
    Isaacs, W B
    Emmert-Buck, M R
    Nykter, M
    Visakorpi, T [ORCID]
    Bova, G S [ORCID]
    Wedge, D C [ORCID]

  2. Author Address

    Big Data Institute, University of Oxford, Old Road Campus, Headington, Oxford, UK., Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, FI, 33014, Finland., Medical and Clinical Genetics and Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Norwich Medical School, University of East Anglia, Norwich, UK., Institute for Molecular Medicine Finland, University of Helsinki, Tukholmankatu 8, FIN-00290, Helsinki, Finland., Cancer Genomic Research Laboratory (CGR), Division of Cancer Epidemiology and Genetics, NCI, FNLCR, Leidos Biomedical Research, Inc, Gaithersburg, MD, USA., Molecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA., Fimlab Laboratories, Department of Pathology, Tampere University Hospital, Tampere, Finland., Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Avoneaux Medical Institute, Baltimore, MD, USA., Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, FI, 33014, Finland. steve.bova@tuni.fi., Big Data Institute, University of Oxford, Old Road Campus, Headington, Oxford, UK. david.wedge@manchester.ac.uk., Oxford NIHR Biomedical Research Centre, Oxford, UK. david.wedge@manchester.ac.uk., Manchester Cancer Research Centre, University of Manchester, Manchester, UK. david.wedge@manchester.ac.uk.,
    1. Year: 2020
    2. Date: OCT 8
    3. Epub Date: 2020 10 08
  2. Journal: Nature communications
    1. 11
    2. 1
    3. Pages: 5070
  4. Type of Article: Article
  5. Article Number: 5070
  6. ISSN: 2041-1723
  1. Abstract:

    The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. We infer detailed reconstructions of tumor phylogenies in ten prostate cancer patients with fatal disease, and investigate them in conjunction with histopathology and tumor DNA extracted from blood and cerebrospinal fluid. Substantial evolution occurs within the prostate, resulting in branching into multiple spatially intermixed lineages. One dominant lineage emerges that initiates and drives systemic metastasis, where polyclonal seeding between sites is common. Routes to metastasis differ between patients, and likely genetic drivers of metastasis distinguish the metastatic lineage from the lineage that remains confined to the prostate within each patient. Body fluids capture features of the dominant lineage, and subclonal expansions that occur in the metastatic phase are non-uniformly represented. Cerebrospinal fluid analysis reveals lineages not detected in blood-borne DNA, suggesting possible clinical utility. The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. Here, the authors use deep genomic sequencing and histopathological information to trace tumor evolution both within the prostate and during metastasis in ten men.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41467-020-18843-5
  3. PMID: 33033260
  4. View record in Web of Science®
  5. WOS: 000581918200001
  6. PII : 10.1038/s41467-020-18843-5

Library Notes

  1. Fiscal Year: FY2020-2021
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