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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Woodcock DJ,Riabchenko E,Taavitsainen S,Kankainen M,Gundem G,Brewer DS,Ellonen P,Lepistö M,Golubeva YA,Warner AC,Tolonen T,Jasu J,Isaacs WB,Emmert-Buck MR,Nykter M,Visakorpi T,Bova GS,Wedge DCdoi
10.1038/s41467-020-18843-5subject
Has Abstractpub_date
2020-10-08 00:00:00pages
5070issue
1issn
2041-1723pii
10.1038/s41467-020-18843-5journal_volume
11pub_type
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