Show simple item record

dc.contributor.authorTurajlic, S
dc.contributor.authorXu, H
dc.contributor.authorLitchfield, K
dc.contributor.authorRowan, A
dc.contributor.authorHorswell, S
dc.contributor.authorChambers, T
dc.contributor.authorO'Brien, T
dc.contributor.authorLopez, JI
dc.contributor.authorWatkins, TBK
dc.contributor.authorNicol, D
dc.contributor.authorStares, M
dc.contributor.authorChallacombe, B
dc.contributor.authorHazell, S
dc.contributor.authorChandra, A
dc.contributor.authorMitchell, TJ
dc.contributor.authorAu, L
dc.contributor.authorEichler-Jonsson, C
dc.contributor.authorJabbar, F
dc.contributor.authorSoultati, A
dc.contributor.authorChowdhury, S
dc.contributor.authorRudman, S
dc.contributor.authorLynch, J
dc.contributor.authorFernando, A
dc.contributor.authorStamp, G
dc.contributor.authorNye, E
dc.contributor.authorStewart, A
dc.contributor.authorXing, W
dc.contributor.authorSmith, JC
dc.contributor.authorEscudero, M
dc.contributor.authorHuffman, A
dc.contributor.authorMatthews, N
dc.contributor.authorElgar, G
dc.contributor.authorPhillimore, B
dc.contributor.authorCosta, M
dc.contributor.authorBegum, S
dc.contributor.authorWard, S
dc.contributor.authorSalm, M
dc.contributor.authorBoeing, S
dc.contributor.authorFisher, R
dc.contributor.authorSpain, L
dc.contributor.authorNavas, C
dc.contributor.authorGrönroos, E
dc.contributor.authorHobor, S
dc.contributor.authorSharma, S
dc.contributor.authorAurangzeb, I
dc.contributor.authorLall, S
dc.contributor.authorPolson, A
dc.contributor.authorVaria, M
dc.contributor.authorHorsfield, C
dc.contributor.authorFotiadis, N
dc.contributor.authorPickering, L
dc.contributor.authorSchwarz, RF
dc.contributor.authorSilva, B
dc.contributor.authorHerrero, J
dc.contributor.authorLuscombe, NM
dc.contributor.authorJamal-Hanjani, M
dc.contributor.authorRosenthal, R
dc.contributor.authorBirkbak, NJ
dc.contributor.authorWilson, GA
dc.contributor.authorPipek, O
dc.contributor.authorRibli, D
dc.contributor.authorKrzystanek, M
dc.contributor.authorCsabai, I
dc.contributor.authorSzallasi, Z
dc.contributor.authorGore, M
dc.contributor.authorMcGranahan, N
dc.contributor.authorVan Loo, P
dc.contributor.authorCampbell, P
dc.contributor.authorLarkin, J
dc.contributor.authorSwanton, C
dc.contributor.authorTRACERx Renal Consortium
dc.date.accessioned2018-06-14T09:33:24Z
dc.date.issued2018-04-12
dc.identifier.citationCell, 2018, 173 (3), pp. 595 - 610.e11
dc.identifier.issn0092-8674
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1871
dc.identifier.eissn1097-4172
dc.identifier.doi10.1016/j.cell.2018.03.043
dc.description.abstractThe evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance.
dc.formatPrint-Electronic
dc.format.extent595 - 610.e11
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectTRACERx Renal Consortium
dc.subjectChromosomes
dc.subjectHumans
dc.subjectCarcinoma, Renal Cell
dc.subjectKidney Neoplasms
dc.subjectNeoplasm Metastasis
dc.subjectDisease Progression
dc.subjectPrognosis
dc.subjectModels, Statistical
dc.subjectLongitudinal Studies
dc.subjectProspective Studies
dc.subjectSequence Analysis, DNA
dc.subjectEvolution, Molecular
dc.subjectPhylogeny
dc.subjectPhenotype
dc.subjectGenetic Heterogeneity
dc.subjectMutation
dc.subjectAlleles
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenetic Variation
dc.subjectClonal Evolution
dc.subjectBiomarkers, Tumor
dc.titleDeterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.
dc.typeJournal Article
dcterms.dateAccepted2018-03-19
rioxxterms.versionofrecord10.1016/j.cell.2018.03.043
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-04-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell
pubs.issue3
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Experimental Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Experimental Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume173
pubs.embargo.termsNot known
icr.researchteamMelanoma and Kidney Canceren_US
icr.researchteamExperimental Pathologyen_US
icr.researchteamMolecular & Population Geneticsen_US
dc.contributor.icrauthorStamp, Gordonen
dc.contributor.icrauthorTurajlic, Samraen
dc.contributor.icrauthorGore, Martinen
dc.contributor.icrauthorLarkin, Jamesen
dc.contributor.icrauthorLitchfield, Kevinen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0