Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue

Cooper, Colin, Eeles, Rosalind A, Wedge, David C, Van Loo, Peter, Gundem, Gunes, Alexandrov, Ludmil B., Kreymer, Barbara, Butler, Adam, Lynch, Andrew, Edwards, Sandra E, Camacho, Niedzica, Massie, Charlie E, Kote-Jarai, Zsofia, Dennis, Nening, Merson, Sue, Leongamornlert, Daniel A, Zamora, Jorge, Kay, Jonathan, Luxton, Hayley J, Corbishley, Cathy, Thomas, Sarah, Nik-Zainal, Serena, O'Meara, Sarah, Matthews, Lucy, Clark, Jeremy, Hurst, Rachel, Mithen (IFR), Richard, Bristow (Ontario Cancer Inst. CA), Rob, Boutros, Paul C, Fraser, Michael, Cooke, Susanna, Raine, Keiran, Jones, David, Menzies, Andrew, Stebbings, Lucy, Hinton, Jon, Teague, Jon, Mclaren, Stuart, Mudie, Laura, Hardy, Claire, Anderson, Elizabeth, Joseph, Olivia, Goody, Victoria, Robinson, Ben, Maddison, Mark, Gamble, Stephen J., Greenman, Christopher, Berney, Dan, Hazell, Steven, Livni, Naomi, Fisher, Cyril, Ogden, Christopher, Kumar, Pardeep, Thompson, Alan, Woodhouse, Christopher J, Nicol, David, Mayer, Erik, Dudderidge, Tim, Shah, Nimish, Gnanapragasam, Vincent, Voet, Thierry, Campbell, Peter, Futreal, P Andrew, Easton, Douglas F, Warren, Anne Y, Foster, Christopher S, Stratton, Michael R, Whitaker, Hayley C, Mcdermott, Ultan, Brewer, Daniel and Neal, David E (2015) Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue. Nature Genetics, 47. 367–372. ISSN 1061-4036

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Abstract

Whole genome 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 on- going 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 tissue 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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Computing Sciences

University of East Anglia > Faculty of Science > Research Groups > Computational Biology (subgroups are shown below) > Analysis and models of genomic variation
Depositing User: Pure Connector
Date Deposited: 09 Mar 2015 07:23
Last Modified: 22 Jul 2020 00:07
URI: https://ueaeprints.uea.ac.uk/id/eprint/52532
DOI: 10.1038/ng.3221

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