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

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Woodcock , D J , Riabchenko , E , Taavitsainen , S , Kankainen , M , Gundem , G , Brewer , D S , Ellonen , P , Lepistö , M , Golubeva , Y A , Warner , A C , Tolonen , T , Jasu , J , Isaacs , W B , Emmert-Buck , M R , Nykter , M , Visakorpi , T , Bova , G S & Wedge , D C 2020 , ' Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy ' , Nature Communications , vol. 11 , no. 1 , 5070 . https://doi.org/10.1038/s41467-020-18843-5

Title: Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy
Author: Woodcock, D. J.; Riabchenko, E.; Taavitsainen, S.; Kankainen, M.; Gundem, G.; Brewer, D. S.; Ellonen, P.; Lepistö, M.; Golubeva, Y. A.; Warner, A. C.; Tolonen, T.; Jasu, J.; Isaacs, W. B.; Emmert-Buck, M. R.; Nykter, M.; Visakorpi, T.; Bova, G. S.; Wedge, D. C.
Contributor: University of Helsinki, HUSLAB
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2020-10-08
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/321665
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.
Subject: MUTATIONAL PROCESSES
COPY NUMBER
ORIGIN
HETEROGENEITY
DIVERSITY
TRACKING
3111 Biomedicine
1184 Genetics, developmental biology, physiology
3122 Cancers
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