Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

Matthew K.H. Hong, Geoff Macintyre, David C. Wedge, Peter Van Loo, Keval Patel, Sebastian Lunke, Ludmil B. Alexandrov, Clare Sloggett, Marek Cmero, Francesco Marass, Dana Tsui, Stefano Mangiola, Andrew Lonie, Haroon Naeem, Nikhil Sapre, Pramit M. Phal, Natalie Kurganovs, Xiaowen Chin, Michael Kerger, Anne Y. Warren, David Neal, Vincent Gnanapragasam, Nitzan Rosenfeld, John S. Pedersen, Andrew Ryan, Izhak Haviv, Anthony J. Costello, Niall M. Corcoran and Christopher M. Hovens ()
Additional contact information
Matthew K.H. Hong: Royal Melbourne Hospital and University of Melbourne
Geoff Macintyre: Centre for Neural Engineering, University of Melbourne
David C. Wedge: Cancer Genome Project, Wellcome Trust Sanger Institute
Peter Van Loo: Cancer Genome Project, Wellcome Trust Sanger Institute
Keval Patel: Cancer Research UK Cambridge Institute, University of Cambridge
Sebastian Lunke: Centre for Translational Pathology, University of Melbourne
Ludmil B. Alexandrov: Cancer Genome Project, Wellcome Trust Sanger Institute
Clare Sloggett: Victorian Life Sciences Computation Initiative, The University of Melbourne
Marek Cmero: Royal Melbourne Hospital and University of Melbourne
Francesco Marass: Cancer Research UK Cambridge Institute, University of Cambridge
Dana Tsui: Cancer Research UK Cambridge Institute, University of Cambridge
Stefano Mangiola: Centre for Neural Engineering, University of Melbourne
Andrew Lonie: Victorian Life Sciences Computation Initiative, The University of Melbourne
Haroon Naeem: Centre for Neural Engineering, University of Melbourne
Nikhil Sapre: Royal Melbourne Hospital and University of Melbourne
Pramit M. Phal: Royal Melbourne Hospital
Natalie Kurganovs: Royal Melbourne Hospital and University of Melbourne
Xiaowen Chin: Royal Melbourne Hospital and University of Melbourne
Michael Kerger: Royal Melbourne Hospital and University of Melbourne
Anne Y. Warren: University Cambridge Hospitals, Addenbrookes Hospital
David Neal: Cancer Research UK Cambridge Institute, University of Cambridge
Vincent Gnanapragasam: Cancer Research UK Cambridge Institute, University of Cambridge
Nitzan Rosenfeld: Cancer Research UK Cambridge Institute, University of Cambridge
John S. Pedersen: TissuPath Specialist Pathology
Andrew Ryan: TissuPath Specialist Pathology
Izhak Haviv: Bar-Ilan University Medical School
Anthony J. Costello: Royal Melbourne Hospital and University of Melbourne
Niall M. Corcoran: Royal Melbourne Hospital and University of Melbourne
Christopher M. Hovens: Royal Melbourne Hospital and University of Melbourne

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal 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 subclonal 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 subclones with metastatic potential which we can detect in the blood.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms7605 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7605

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms7605

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().