Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04

AUTHORS

Colin S Cooper, Rosalind Eeles, David C Wedge, Peter Van Loo, Gunes Gundem, Ludmil B Alexandrov, Barbara Kremeyer, Adam Butler, Andrew G Lynch, Niedzica Camacho, Charlie E Massie, Jonathan Kay, Hayley J Luxton, Sandra Edwards, Zsofia Kote-Jarai, Nening Dennis, Sue Merson, Daniel Leongamornlert, Jorge Zamora, Cathy Corbishley, Sarah Thomas, Serena Nik-Zainal, Manasa Ramakrishna, Sarah O'Meara, Lucy Matthews, Jeremy Clark, Rachel Hurst, Richard Mithen, Robert G Bristow, Paul C Boutros, Michael Fraser, Susanna Cooke, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Hinton, Jon Teague, Stuart McLaren, Laura Mudie, Claire Hardy, Elizabeth Anderson, Olivia Joseph, Victoria Goody, Ben Robinson, Mark Maddison, Stephen Gamble, Christopher Greenman, Dan Berney, Steven Hazell, Naomi Livni, ICGC Prostate Group, Cyril Fisher, Christopher Ogden, Pardeep Kumar, Alan Thompson, Christopher Woodhouse, David Nicol, Erik Mayer, Tim Dudderidge, Nimish C Shah, Vincent Gnanapragasam, Thierry Voet, Peter Campbell, Andrew Futreal, Douglas Easton, Anne Y Warren, Christopher S Foster, Michael R Stratton, Hayley C Whitaker, Ultan McDermott, Daniel S Brewer, David E Neal

ABSTRACT

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases. More... »

PAGES

367-372

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3221

DOI

http://dx.doi.org/10.1038/ng.3221

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024712684

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25730763


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