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dc.contributor.authorGerstung, Moritz
dc.contributor.authorJolly, Clemency
dc.contributor.authorLeshchiner, Ignaty
dc.contributor.authorDentro, Stefan C
dc.contributor.authorGonzalez, Santiago
dc.contributor.authorRosebrock, Daniel
dc.contributor.authorMitchell, Thomas J
dc.contributor.authorRubanova, Yulia
dc.contributor.authorAnur, Pavana
dc.contributor.authorYu, Kaixian
dc.contributor.authorTarabichi, Maxime
dc.contributor.authorDeshwar, Amit
dc.contributor.authorWintersinger, Jeff
dc.contributor.authorKleinheinz, Kortine
dc.contributor.authorVázquez-García, Ignacio
dc.contributor.authorHaase, Kerstin
dc.contributor.authorJerman, Lara
dc.contributor.authorSengupta, Subhajit
dc.contributor.authorMacintyre, Geoff
dc.contributor.authorMalikic, Salem
dc.contributor.authorDonmez, Nilgun
dc.contributor.authorLivitz, Dimitri G
dc.contributor.authorCmero, Marek
dc.contributor.authorDemeulemeester, Jonas
dc.contributor.authorSchumacher, Steven
dc.contributor.authorFan, Yu
dc.contributor.authorYao, Xiaotong
dc.contributor.authorLee, Juhee
dc.contributor.authorSchlesner, Matthias
dc.contributor.authorBoutros, Paul C
dc.contributor.authorBowtell, David D
dc.contributor.authorZhu, Hongtu
dc.contributor.authorGetz, Gad
dc.contributor.authorImielinski, Marcin
dc.contributor.authorBeroukhim, Rameen
dc.contributor.authorSahinalp, S Cenk
dc.contributor.authorJi, Yuan
dc.contributor.authorPeifer, Martin
dc.contributor.authorMarkowetz, Florian
dc.contributor.authorMustonen, Ville
dc.contributor.authorYuan, Ke
dc.contributor.authorWang, Wenyi
dc.contributor.authorMorris, Quaid D
dc.contributor.authorPCAWG Evolution & Heterogeneity Working Group
dc.contributor.authorSpellman, Paul T
dc.contributor.authorWedge, David C
dc.contributor.authorVan Loo, Peter
dc.contributor.authorPCAWG Consortium
dc.date.accessioned2021-02-04T16:25:47Z
dc.date.available2021-02-04T16:25:47Z
dc.date.issued2020-02
dc.date.submitted2017-08-11
dc.identifier.issn0028-0836
dc.identifier.others41586-019-1907-7
dc.identifier.other1907
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/317163
dc.description.abstractCancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectArticle
dc.subject/631/67/69
dc.subject/631/114
dc.subject/631/181/735
dc.subject/692/699/67/69
dc.subject/45/23
dc.subjectarticle
dc.titleThe evolutionary history of 2,658 cancers.
dc.typeArticle
dc.date.updated2021-02-04T16:25:46Z
prism.endingPage128
prism.issueIdentifier7793
prism.publicationNameNature
prism.startingPage122
prism.volume578
dc.identifier.doi10.17863/CAM.64274
dcterms.dateAccepted2019-11-18
rioxxterms.versionofrecord10.1038/s41586-019-1907-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMarkowetz, Florian [0000-0002-2784-5308]
dc.identifier.eissn1476-4687
pubs.funder-project-idMedical Research Council (MR/L016311/1)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idCancer Research UK (19274)
pubs.funder-project-idCancer Research UK (A19274)
cam.issuedOnline2020-02-06


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)