@article{cc80002b9ad8403f8a3c50c626c0b327,
title = "Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy",
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.",
author = "Woodcock, {D. J.} and E. Riabchenko and S. Taavitsainen and M. Kankainen and G. Gundem and Brewer, {D. S.} and P. Ellonen and M. Lepist{\"o} and Golubeva, {Y. A.} and Warner, {A. C.} and T. Tolonen and J. Jasu and Isaacs, {W. B.} and Emmert-Buck, {M. R.} and M. Nykter and T. Visakorpi and Bova, {G. S.} and Wedge, {D. C.}",
note = "Funding Information: We thank the men and their families who participated in the PELICAN (Project to ELIminate lethal CANcer) integrated clinical-molecular autopsy study of prostate cancer. We thank M. A. Eisenberger, M. A. Carducci, V. Sinibaldi, T. B. Smyth, and G. J. Mamo for oncologic and urologic clinical support; P. Martikainen, R. Kylatie, M. Pirinen, A. Koskenalho, J. Silander, G. Hutchins, and B. Crain for technical support; and ICGC Prostate Cancer UK study group members for support for the prior Gundem et al. Nature 2015 study which serves as a foundation for the current work. Computation was supported by the Finnish Institute for Molecular Medicine, Helsinki, Finland, Tampere University, Tampere, Finland, and the Oxford Biomedical Research Computing (BMRC) facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and the NIHR Oxford Biomedical Research Centre, Oxford, UK. The study was financially supported by The Academy of Finland (2011–present); Cancer Society of Finland (2013–present); Sigrid Juselius Foundation (2016–present), Cancer Research UK (2011–2014), NIHR Oxford BRC (2015–present), Li Ka Shing foundation (2016–present), NCI Intramural Program (2013–2014); PELICAN Autopsy Study family members and friends (1998–2004); John and Kathe Dyson (2000); US National Cancer Institute CA92234 (2000–2005); American Cancer Society (1998–2000); Johns Hopkins University Department of Pathology (1997–2011); Women{\textquoteright}s Board of Johns Hopkins Hospital (1998); The Grove Foundation (1998); Association for the Cure of Cancer of the Prostate (1994–1998); American Foundation for Urologic Disease (1991–1994). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR and the Department of Health. This research was supported by the NIH Intramural Research Program. The project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
doi = "10.1038/s41467-020-18843-5",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
