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

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cam.issuedOnline2015-03-02
dc.contributor.authorCooper, Colin S
dc.contributor.authorEeles, Rosalind
dc.contributor.authorWedge, David C
dc.contributor.authorVan Loo, Peter
dc.contributor.authorGundem, Gunes
dc.contributor.authorAlexandrov, Ludmil B
dc.contributor.authorKremeyer, Barbara
dc.contributor.authorButler, Adam
dc.contributor.authorLynch, Andrew G
dc.contributor.authorCamacho, Niedzica
dc.contributor.authorMassie, Charlie E
dc.contributor.authorKay, Jonathan
dc.contributor.authorLuxton, Hayley J
dc.contributor.authorEdwards, Sandra
dc.contributor.authorKote-Jarai, ZSofia
dc.contributor.authorDennis, Nening
dc.contributor.authorMerson, Sue
dc.contributor.authorLeongamornlert, Daniel
dc.contributor.authorZamora, Jorge
dc.contributor.authorCorbishley, Cathy
dc.contributor.authorThomas, Sarah
dc.contributor.authorNik-Zainal, Serena
dc.contributor.authorO'Meara, Sarah
dc.contributor.authorMatthews, Lucy
dc.contributor.authorClark, Jeremy
dc.contributor.authorHurst, Rachel
dc.contributor.authorMithen, Richard
dc.contributor.authorBristow, Robert G
dc.contributor.authorBoutros, Paul C
dc.contributor.authorFraser, Michael
dc.contributor.authorCooke, Susanna
dc.contributor.authorRaine, Keiran
dc.contributor.authorJones, David
dc.contributor.authorMenzies, Andrew
dc.contributor.authorStebbings, Lucy
dc.contributor.authorHinton, Jon
dc.contributor.authorTeague, Jon
dc.contributor.authorMcLaren, Stuart
dc.contributor.authorMudie, Laura
dc.contributor.authorHardy, Claire
dc.contributor.authorAnderson, Elizabeth
dc.contributor.authorJoseph, Olivia
dc.contributor.authorGoody, Victoria
dc.contributor.authorRobinson, Ben
dc.contributor.authorMaddison, Mark
dc.contributor.authorGamble, Stephen
dc.contributor.authorGreenman, Christopher
dc.contributor.authorBerney, Dan
dc.contributor.authorHazell, Steven
dc.contributor.authorLivni, Naomi
dc.contributor.authorICGC Prostate Group
dc.contributor.authorFisher, Cyril
dc.contributor.authorOgden, Christopher
dc.contributor.authorKumar, Pardeep
dc.contributor.authorThompson, Alan
dc.contributor.authorWoodhouse, Christopher
dc.contributor.authorNicol, David
dc.contributor.authorMayer, Erik
dc.contributor.authorDudderidge, Tim
dc.contributor.authorShah, Nimish C
dc.contributor.authorGnanapragasam, Vincent
dc.contributor.authorVoet, Thierry
dc.contributor.authorCampbell, Peter
dc.contributor.authorFutreal, Andrew
dc.contributor.authorEaston, Douglas
dc.contributor.authorWarren, Anne Y
dc.contributor.authorFoster, Christopher S
dc.contributor.authorStratton, Michael R
dc.contributor.authorWhitaker, Hayley C
dc.contributor.authorMcDermott, Ultan
dc.contributor.authorBrewer, Daniel S
dc.contributor.authorNeal, David E
dc.contributor.orcidLynch, Andy [0000-0002-7876-7338]
dc.contributor.orcidMassie, Charles [0000-0003-2314-4843]
dc.contributor.orcidNik-Zainal, Serena [0000-0001-5054-1727]
dc.contributor.orcidGnanapragasam, Vincent [0000-0003-4722-4207]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.contributor.orcidWarren, Anne [0000-0002-1170-7867]
dc.date.accessioned2018-11-01T14:03:18Z
dc.date.available2018-11-01T14:03:18Z
dc.date.issued2015-04
dc.description.abstractGenome-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.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.31890
dc.identifier.eissn1546-1718
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284515
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/ng.3221
dc.subjectCase-Control Studies
dc.subjectCell Lineage
dc.subjectClonal Evolution
dc.subjectClone Cells
dc.subjectDNA Mutational Analysis
dc.subjectHumans
dc.subjectMale
dc.subjectMutation
dc.subjectNeoplasms, Multiple Primary
dc.subjectPhylogeny
dc.subjectProstate
dc.subjectProstatic Neoplasms
dc.titleAnalysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.
dc.typeArticle
dcterms.dateAccepted2015-01-21
prism.endingPage372
prism.issueIdentifier4
prism.publicationDate2015
prism.publicationNameNat Genet
prism.startingPage367
prism.volume47
pubs.funder-project-idCancer Research UK (via Institute of Cancer Research (ICR)) (C5047/A22530)
pubs.funder-project-idCancer Research UK (via Institute of Cancer Research (ICR)) (C5047/A14835)
rioxxterms.licenseref.startdate2015-04
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1038/ng.3221

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