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dc.contributor.authorMourikis, Thanos P.en
dc.contributor.authorBenedetti, Lorenaen
dc.contributor.authorFoxall, Elizabethen
dc.contributor.authorTemelkovski, Damjanen
dc.contributor.authorNulsen, Joelen
dc.contributor.authorPerner, Julianeen
dc.contributor.authorCereda, Matteoen
dc.contributor.authorLagergren, Jesperen
dc.contributor.authorHowell, Michaelen
dc.contributor.authorYau, Christopheren
dc.contributor.authorFitzgerald, Rebecca C.en
dc.contributor.authorScaffidi, Paolaen
dc.contributor.authorCiccarelli, Francesca D.en
dc.contributor.authorNoorani, Ayeshaen
dc.contributor.authorEdwards, Paul A. W.en
dc.contributor.authorElliott, Rachael Felsen
dc.contributor.authorGrehan, Nicolaen
dc.contributor.authorNutzinger, Barbaraen
dc.contributor.authorHughes, Caitrionaen
dc.contributor.authorFidziukiewicz, Elwiraen
dc.contributor.authorBornschein, Janen
dc.contributor.authorMacRae, Shonaen
dc.contributor.authorCrawte, Jasonen
dc.contributor.authorNorthrop, Alexen
dc.contributor.authorContino, Gianmarcoen
dc.contributor.authorLi, Xiaodunen
dc.contributor.authorde la Rue, Rachelen
dc.contributor.authorKatz-Summercorn, Annaliseen
dc.contributor.authorAbbas, Sujathen
dc.contributor.authorLoureda, Danielen
dc.contributor.authorO’Donovan, Mariaen
dc.contributor.authorMiremadi, Ahmaden
dc.contributor.authorMalhotra, Shalinien
dc.contributor.authorTripathi, Monikaen
dc.contributor.authorTavaré, Simonen
dc.contributor.authorLynch, Andy G.en
dc.contributor.authorEldridge, Matthewen
dc.contributor.authorSecrier, Mariaen
dc.contributor.authorBower, Lawrenceen
dc.contributor.authorDevonshire, Ginnyen
dc.contributor.authorJammula, Sriganeshen
dc.contributor.authorDavies, Jimen
dc.contributor.authorCrichton, Charlesen
dc.contributor.authorCarroll, Nicken
dc.contributor.authorSafranek, Peteren
dc.contributor.authorHindmarsh, Andrewen
dc.contributor.authorSujendran, Vijayendranen
dc.contributor.authorHayes, Stephen J.en
dc.contributor.authorAng, Yengen
dc.contributor.authorSharrocks, Andrewen
dc.contributor.authorPreston, Shaun R.en
dc.contributor.authorOakes, Sarahen
dc.contributor.authorBagwan, Izharen
dc.contributor.authorSave, Vickien
dc.contributor.authorSkipworth, Richard J. E.en
dc.contributor.authorHupp, Ted R.en
dc.contributor.authorRobert O’Neill, J.en
dc.contributor.authorTucker, Olgaen
dc.contributor.authorBeggs, Andrewen
dc.contributor.authorTaniere, Philippeen
dc.contributor.authorPuig, Soniaen
dc.contributor.authorUnderwood, Timothy J.en
dc.contributor.authorWalker, Robert C.en
dc.contributor.authorGrace, Ben L.en
dc.contributor.authorBarr, Hughen
dc.contributor.authorShepherd, Neilen
dc.contributor.authorOld, Oliveren
dc.contributor.authorGossage, Jamesen
dc.contributor.authorDavies, Andrewen
dc.contributor.authorChang, Fujuen
dc.contributor.authorZylstra, Janineen
dc.contributor.authorMahadeva, Ulaen
dc.contributor.authorGoh, Vickyen
dc.contributor.authorSanders, Granten
dc.contributor.authorBerrisford, Richarden
dc.contributor.authorHarden, Catherineen
dc.contributor.authorLewis, Mikeen
dc.contributor.authorCheong, Eden
dc.contributor.authorKumar, Bhaskaren
dc.contributor.authorParsons, Simon L.en
dc.contributor.authorSoomro, Irshaden
dc.contributor.authorKaye, Philipen
dc.contributor.authorSaunders, Johnen
dc.contributor.authorLovat, Laurenceen
dc.contributor.authorHaidry, Rehanen
dc.contributor.authorIgali, Laszloen
dc.contributor.authorScott, Michaelen
dc.contributor.authorSothi, Sharmilaen
dc.contributor.authorSuortamo, Sarien
dc.contributor.authorLishman, Suzyen
dc.contributor.authorHanna, George B.en
dc.contributor.authorPeters, Christopher J.en
dc.contributor.authorMoorthy, Krishnaen
dc.contributor.authorGrabowska, Annaen
dc.contributor.authorTurkington, Richarden
dc.contributor.authorMcManus, Damianen
dc.contributor.authorKhoo, Daviden
dc.contributor.authorFickling, Willen
dc.date.accessioned2020-07-14T15:11:50Z
dc.date.available2020-07-14T15:11:50Z
dc.date.issued2019-07-15
dc.date.submitted2018-11-09
dc.identifier.others41467-019-10898-3
dc.identifier.other10898
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/307928
dc.description.abstractAbstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/67
dc.subject/631/67/69
dc.subject/631/67/1504/1477
dc.subject/13/44
dc.subject/13/31
dc.subject/13/109
dc.subject/38/22
dc.subject/38/23
dc.subject/38/77
dc.subject/38/88
dc.subject/38/90
dc.subjectarticle
dc.titlePatient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
dc.typeArticle
dc.date.updated2020-07-14T15:11:49Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume10
dc.identifier.doi10.17863/CAM.55020
dcterms.dateAccepted2019-06-04
rioxxterms.versionofrecord10.1038/s41467-019-10898-3
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMourikis, Thanos P. [0000-0002-8026-8837]
dc.contributor.orcidFoxall, Elizabeth [0000-0003-1995-5547]
dc.contributor.orcidScaffidi, Paola [0000-0002-3642-4193]
dc.identifier.eissn2041-1723


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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)