@article{Cooper2015, 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.}, author = {Cooper, Colin S. and van Loo, Peter and Eeles, Rosalind and Wedge, David C. and Gundem, Gunes and Alexandrov, Ludmil B. and Kremeyer, Barbara and Butler, Adam and Lynch, Andrew G. and Camacho, Niedzica and Massie, Charlie E. and Kay, Jonathan and Luxton, Hayley J. and Edwards, Sandra and Kote-Jarai, ZSofia and Dennis, Nening and Merson, Sue and Leongamornlert, Daniel and Zamora, Jorge and Corbishley, Cathy and Thomas, Sarah and Nik-Zainal, Serena and O'Meara, Sarah and O’Meara, Sarah and Matthews, Lucy and Clark, Jeremy and Hurst, Rachel and Mithen, Richard and Bristow, Robert G. and Boutros, Paul C. and Fraser, Michael and Cooke, Susanna and Raine, Keiran and Jones, David and Menzies, Andrew and Stebbings, Lucy and Hinton, Jon and Teague, Jon and McLaren, Stuart and Mudie, Laura and Hardy, Claire and Anderson, Elizabeth and Joseph, Olivia and Goody, Victoria and Robinson, Ben and Maddison, Mark and Gamble, Stephen and Greenman, Christopher and Berney, Dan and Hazell, Steven and Livni, Naomi and Group, Icgc Prostate and Fisher, Cyril and Ogden, Christopher and Kumar, Pardeep and Thompson, Alan and Woodhouse, Christopher and Nicol, David and Mayer, Erik and Dudderidge, Tim and Shah, Nimish C. and Gnanapragasam, Vincent and Voet, Thierry and Campbell, Peter and Futreal, Andrew and Easton, Douglas and Warren, Anne Y. and Foster, Christopher S. and Stratton, Michael R. and Whitaker, Hayley C. and McDermott, Ultan and Brewer, Daniel S. and Neal, David E.}, doi = {10.1038/ng.3221}, journal = {Nature Genetics}, month = {mar}, pages = {367-372}, title = {Analysis of the Genetic Phylogeny of Multifocal Prostate Cancer Identifies Multiple Independent Clonal Expansions in Neoplastic and Morphologically Normal Prostate Tissue}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380509/}, volume = {47}, year = {2015} }