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Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer.
Hong, Matthew K H; Macintyre, Geoff; Wedge, David C; Van Loo, Peter; Patel, Keval; Lunke, Sebastian; Alexandrov, Ludmil B; Sloggett, Clare; Cmero, Marek; Marass, Francesco; Tsui, Dana; Mangiola, Stefano; Lonie, Andrew; Naeem, Haroon; Sapre, Nikhil; Phal, Pramit M; Kurganovs, Natalie; Chin, Xiaowen; Kerger, Michael; Warren, Anne Y; Neal, David; Gnanapragasam, Vincent; Rosenfeld, Nitzan; Pedersen, John S; Ryan, Andrew; Haviv, Izhak; Costello, Anthony J; Corcoran, Niall M; Hovens, Christopher M.
Afiliação
  • Hong MK; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
  • Macintyre G; 1] Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia [2] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [3] Diagnostic Genomics, NICTA, Victoria Research Laboratory, The
  • Wedge DC; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
  • Van Loo P; 1] Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Department of Human Genetics, KU Leuven, Herestraat 49 Box 602, B-3000 Leuven, Belgium [3] Cancer Research UK London Research Institute, London WC2A 3LY, UK.
  • Patel K; 1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
  • Lunke S; Centre for Translational Pathology, University of Melbourne, Parkville 3050, Victoria, Australia.
  • Alexandrov LB; 1] Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
  • Sloggett C; Victorian Life Sciences Computation Initiative, The University of Melbourne, Parkville 3050, Victoria, Australia.
  • Cmero M; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia [3] Centre for Neural Engineering, Department of Computing and Information Sy
  • Marass F; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Tsui D; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Mangiola S; Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
  • Lonie A; Victorian Life Sciences Computation Initiative, The University of Melbourne, Parkville 3050, Victoria, Australia.
  • Naeem H; 1] Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia [2] Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne, Parkville, Victoria 3010, Australia.
  • Sapre N; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
  • Phal PM; Department of Radiology, Royal Melbourne Hospital, Parkville 3050, Victoria, Australia.
  • Kurganovs N; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
  • Chin X; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
  • Kerger M; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
  • Warren AY; Department of Histopathology, University Cambridge Hospitals, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ, UK.
  • Neal D; 1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
  • Gnanapragasam V; 1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
  • Rosenfeld N; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Pedersen JS; 1] TissuPath Specialist Pathology, Mount Waverley 3149, Victoria, Australia [2] Monash University Faculty of Medicine, Clayton 3168, Victoria, Australia.
  • Ryan A; TissuPath Specialist Pathology, Mount Waverley 3149, Victoria, Australia.
  • Haviv I; Bar-Ilan University Medical School, Safad 1311502, Israel.
  • Costello AJ; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
  • Corcoran NM; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
  • Hovens CM; 1] Department of Surgery, Division of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville 3050, Victoria, Australia [2] The Epworth Prostate Centre, Epworth Hospital, Richmond 3121, Victoria, Australia.
Nat Commun ; 6: 6605, 2015 Apr 01.
Article em En | MEDLINE | ID: mdl-25827447
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias Ósseas / Neoplasias Encefálicas / Adenocarcinoma / Proteína Supressora de Tumor p53 Idioma: En Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Austrália
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias Ósseas / Neoplasias Encefálicas / Adenocarcinoma / Proteína Supressora de Tumor p53 Idioma: En Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Austrália