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Title: Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer.
Epworth Authors: Hong, Matthew
Cmero, Marek
Sapre, Nikhil
Kurganovs, Natalie
Chin, Xiaowin
Kerger, Michael
Costello, Anthony
Corcoran, Niall
Hovens, Christopher
Other Authors: Macintyre, Geoff
Wedge, David
Van Loo, Peter
Patel, Keval
Lunke, Sebastian
Alexandrov, Ludmil
Sloggett, Clare
Marass, Francesco
Tsui, Dana
Mangiola, Stefano
Lonie, Andrew
Naeem, Haroon
Phal, Pramit
Warren, Anne
Neal, David
Gnanapragasam, Vincent
Rosenfield, Nitsan
Pedersen, John
Ryan, Andrew
Haviv, Izhak
Keywords: The Epworth Prostate Centre, Epworth Hospital, Victoria, Australia.
Prostate Cancer
Cancer of the Prostate
Neoplasms, Prostate
Prostate Neoplasms
Neoplasm Seeding
Seeding, Neoplasm
Tissue Procurement
Subclonal Diversity
Metastatic Tumors
Metastatic Potential
Issue Date: Apr-2015
Publisher: Nature Publishing Group
Citation: Nature Communications. 2015 Apr 1;6:6605.
Abstract: Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the sub-clonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of sub-clonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of sub-clones with metastatic potential which we can detect in the blood.
DOI: 10.1038/ncomms7605
PubMed URL:
ISSN: 2041-1723
Journal Title: Nature Communications
Type: Journal Article
Affiliated Organisations: Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, Australia.
Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Victoria Research Laboratory, The University of Melbourne, Parkville, Victoria 3010, Australia.
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Department of Human Genetics, KU Leuven, Herestraat Leuven, Belgium.
Cancer Research UK London Research Institute, London, UK.
Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge, UK
Centre for Translational Pathology, University of Melbourne, Parkville, Victoria, Australia
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Victorian Life Sciences Computation Initiative, The University of Melbourne, Parkville, Victoria, Australia.
Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne, Parkville, Victoria, Australia.
Department of Radiology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Department of Histopathology, University Cambridge Hospitals, Addenbrookes Hospital, Hills Road, Cambridge, UK.
TissuPath Specialist Pathology, Mount Waverley, Victoria, Australia.
Monash University Faculty of Medicine, Clayton, Victoria, Australia.
Bar-Ilan University Medical School, Safad, Israel.
Type of Clinical Study or Trial: Cohort Study
Appears in Collections:Cancer Services
Epworth Prostate Centre
UroRenal, Vascular

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