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

• DOI: 10.1038/ncomms7605
• Publication Date: 2015-04-01T12:11:31Z
• Authors: 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 Gnanaprag...; Nitzan Rosenfeld; John S. Pedersen; Andrew Ryan; Izhak Haviv; Anthony J. Costello; Niall M. Corcoran; Christopher M. Ho...
• Keywords: Primary tumor; Chromoplexy

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 poorly understood. Here we reveal precise direction metastatic spread across four lethal patients using whole-genome ultra-deep targeted sequencing longitudinally collected tumours. We find one case surgical bed causing local recurrence, another cross-metastatic site seeding combining with dynamic remoulding mixtures response therapy. By end-stage blood, detect both tumour clones, even years after removal prostate. Analysis mutations associated reveals an enrichment TP53 mutations, additional metastases from 19 demonstrates that acquisition linked expansion subclones potential which can blood.