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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

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dc.contributor.authorKang, Eun-Young
dc.contributor.authorWeir, Ashley
dc.contributor.authorMeagher, Nicola S
dc.contributor.authorFarrington, Kyo
dc.contributor.authorNelson, Gregg S
dc.contributor.authorGhatage, Prafull
dc.contributor.authorLee, Cheng-Han
dc.contributor.authorRiggan, Marjorie J
dc.contributor.authorBolithon, Adelyn
dc.contributor.authorPopovic, Gordana
dc.contributor.authorLeung, Betty
dc.contributor.authorTang, Katrina
dc.contributor.authorLambie, Neil
dc.contributor.authorMillstein, Joshua
dc.contributor.authorAlsop, Jennifer
dc.contributor.authorAnglesio, Michael S
dc.contributor.authorAtaseven, Beyhan
dc.contributor.authorBarlow, Ellen
dc.contributor.authorBeckmann, Matthias W
dc.contributor.authorBerger, Jessica
dc.contributor.authorBisinotto, Christiani
dc.contributor.authorBösmüller, Hans
dc.contributor.authorBoros, Jessica
dc.contributor.authorBrand, Alison H
dc.contributor.authorBrooks-Wilson, Angela
dc.contributor.authorBrucker, Sara Y
dc.contributor.authorCarney, Michael E
dc.contributor.authorCasablanca, Yovanni
dc.contributor.authorCazorla-Jiménez, Alicia
dc.contributor.authorCohen, Paul A
dc.contributor.authorConrads, Thomas P
dc.contributor.authorCook, Linda S
dc.contributor.authorCoulson, Penny
dc.contributor.authorCourtney-Brooks, Madeleine
dc.contributor.authorCramer, Daniel W
dc.contributor.authorCrowe, Philip
dc.contributor.authorCunningham, Julie M
dc.contributor.authorCybulski, Cezary
dc.contributor.authorDarcy, Kathleen M
dc.contributor.authorEl-Bahrawy, Mona A
dc.contributor.authorElishaev, Esther
dc.contributor.authorErber, Ramona
dc.contributor.authorFarrell, Rhonda
dc.contributor.authorFereday, Sian
dc.contributor.authorFischer, Anna
dc.contributor.authorGarcía, María J
dc.contributor.authorGayther, Simon A
dc.contributor.authorGentry-Maharaj, Aleksandra
dc.contributor.authorGilks, C Blake
dc.contributor.authorGrube, Marcel
dc.contributor.authorHarnett, Paul R
dc.contributor.authorHarrington, Shariska Petersen
dc.contributor.authorHarter, Philipp
dc.contributor.authorHartmann, Arndt
dc.contributor.authorHecht, Jonathan L
dc.contributor.authorHeikaus, Sebastian
dc.contributor.authorHein, Alexander
dc.contributor.authorHeitz, Florian
dc.contributor.authorHendley, Joy
dc.contributor.authorHernandez, Brenda Y
dc.contributor.authorPolo, Susanna Hernando
dc.contributor.authorHeublein, Sabine
dc.contributor.authorHirasawa, Akira
dc.contributor.authorHøgdall, Estrid
dc.contributor.authorHøgdall, Claus K
dc.contributor.authorHorlings, Hugo M
dc.contributor.authorHuntsman, David G
dc.contributor.authorHuzarski, Tomasz
dc.contributor.authorJewell, Andrea
dc.contributor.authorJimenez-Linan, Mercedes
dc.contributor.authorJones, Michael E
dc.contributor.authorKaufmann, Scott H
dc.contributor.authorKennedy, Catherine J
dc.contributor.authorKhabele, Dineo
dc.contributor.authorKommoss, Felix K F
dc.contributor.authorKruitwagen, Roy F P M
dc.contributor.authorLambrechts, Diether
dc.contributor.authorLe, Nhu D
dc.contributor.authorLener, Marcin
dc.contributor.authorLester, Jenny
dc.contributor.authorLeung, Yee
dc.contributor.authorLinder, Anna
dc.contributor.authorLoverix, Liselore
dc.contributor.authorLubiński, Jan
dc.contributor.authorMadan, Rashna
dc.contributor.authorMaxwell, G Larry
dc.contributor.authorModugno, Francesmary
dc.contributor.authorNeuhausen, Susan L
dc.contributor.authorOlawaiye, Alexander
dc.contributor.authorOlbrecht, Siel
dc.contributor.authorOrsulic, Sandra
dc.contributor.authorPalacios, José
dc.contributor.authorPearce, Celeste Leigh
dc.contributor.authorPike, Malcolm C
dc.contributor.authorQuinn, Carmel M
dc.contributor.authorMohan, Ganendra Raj
dc.contributor.authorRodríguez-Antona, Cristina
dc.contributor.authorRuebner, Matthias
dc.contributor.authorRyan, Andy
dc.contributor.authorSalfinger, Stuart G
dc.contributor.authorSasamoto, Naoko
dc.contributor.authorSchildkraut, Joellen M
dc.contributor.authorSchoemaker, Minouk J
dc.contributor.authorShah, Mitul
dc.contributor.authorSharma, Raghwa
dc.contributor.authorShvetsov, Yurii B
dc.contributor.authorSingh, Naveena
dc.contributor.authorSonke, Gabe S
dc.contributor.authorSteele, Linda
dc.contributor.authorStewart, Colin J R
dc.contributor.authorSundfeldt, Karin
dc.contributor.authorSwerdlow, Anthony J
dc.contributor.authorTalhouk, Aline
dc.contributor.authorTan, Adeline
dc.contributor.authorTaylor, Sarah E
dc.contributor.authorTerry, Kathryn L
dc.contributor.authorTołoczko, Aleksandra
dc.contributor.authorTraficante, Nadia
dc.contributor.authorVan de Vijver, Koen K
dc.contributor.authorvan der Aa, Maaike A
dc.contributor.authorVan Gorp, Toon
dc.contributor.authorVan Nieuwenhuysen, Els
dc.contributor.authorvan-Wagensveld, Lilian
dc.contributor.authorVergote, Ignace
dc.contributor.authorVierkant, Robert A
dc.contributor.authorWang, Chen
dc.contributor.authorWilkens, Lynne R
dc.contributor.authorWinham, Stacey J
dc.contributor.authorWu, Anna H
dc.contributor.authorBenitez, Javier
dc.contributor.authorBerchuck, Andrew
dc.contributor.authorCandido Dos Reis, Francisco J
dc.contributor.authorDeFazio, Anna
dc.contributor.authorFasching, Peter A
dc.contributor.authorGoode, Ellen L
dc.contributor.authorGoodman, Marc T
dc.contributor.authorGronwald, Jacek
dc.contributor.authorKarlan, Beth Y
dc.contributor.authorKommoss, Stefan
dc.contributor.authorMenon, Usha
dc.contributor.authorSinn, Hans-Peter
dc.contributor.authorStaebler, Annette
dc.contributor.authorBrenton, James D
dc.contributor.authorBowtell, David D
dc.contributor.authorPharoah, Paul D P
dc.contributor.authorRamus, Susan J
dc.contributor.authorKöbel, Martin
dc.contributor.funderNational Health & Medical Research Council (NHMRC)
dc.contributor.funderTranslational Cancer Research Network
dc.contributor.funderUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA
dc.contributor.funderNIH National Cancer Institute (NCI)
dc.contributor.funderHeuer Stiftung fur medizinische Forschung
dc.contributor.funderJanet D. Cottrelle Foundation Scholars program
dc.contributor.funderMichael Smith Foundation for Health Research
dc.contributor.funderFWO
dc.contributor.funderUK Research & Innovation (UKRI)
dc.contributor.funderGerman Research Foundation (DFG)
dc.contributor.funderMedical Research Council UK (MRC)
dc.date.accessioned2025-03-20T06:55:12Z
dc.date.available2025-03-20T06:55:12Z
dc.date.issued2023-03-01
dc.descriptionS. Ramus is supported by National Health and Medical Research Council of Australia (NHMRC) grant APP2009840. N.S. Meagher is supported by the NSW Ministry of Health and UNSW Sydney under the NSW Health PhD Scholarship Program, and the Translational Cancer Research Network, a translational cancer research center program funded by the Cancer Institute NSW. J. Millstein is funded by NCI grant P30CA014089. S. Heublein was funded by Heuer Stiftung fur medizinische Forschung. M.S. Anglesio is funded through a Michael Smith Foundation for Health Research Scholar Award and the Janet D. Cottrelle Foundation Scholars program managed by the BC Cancer Foundation. BC's Gynecological Cancer Research team (OVCARE) receives support through the BC Cancer Foundation and The VGH+UBC Hospital Foundation. L. Loverix is predoctoral researcher of the Fund for Scientific Research-Flanders (FWO Vlaanderen 1S41921). T. Van Gorp is a Senior Clinical Investigator of the Fund for Scientific Research-Flanders (FWO Vlaanderen 18B2921N). The funding for K.M. Darcy and preparation of tumor samples and clinical samples are from awards HU0001-16-2-0006 and HU0001-21-2-0027 from the Uniformed Services University of the Health Sciences from the Defense Health Program to the Henry M Jackson Foundation (HJF) for the Advancement of Military Medicine Inc. Gynecologic Cancer Center of Excellence Program (PI: Yovanni Casablanca, Co-PI: G. Larry Maxwell). D. Khabele is supported by NIH NCI grants R01CA243511 and R21CA210210. A. Staebler received funding by Deutsche Forschungsgemeinschaft as part of the CRC 685. R.E. was supported by the Interdisciplinary Center for Clinical Research (IZKF; Clinician Scientist Program) of the Medical Faculty FAU Erlangen-Nurnberg. U. Menon and A. Gentry-Maharaj are supported by salary contributions through MRC core funding (MC_UU_00004/01).
dc.description.abstractCyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.
dc.description.abstractWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.
dc.description.abstractHigh-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.
dc.description.abstractThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
dc.description.peerreviewedSí
dc.format.number5
dc.format.page697-713
dc.format.volume129
dc.identifier.citationCancer . 2023 Mar 1;129(5):697-713.
dc.identifier.journalCancer
dc.identifier.pubmedID36572991
dc.identifier.urihttps://hdl.handle.net/20.500.12105/26529
dc.language.isoeng
dc.publisherWiley
dc.relation.publisherversionhttp:// DOI: 10.1002/cncr.34582
dc.repisalud.institucionCNIO
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Genética Humana
dc.rights.accessRightsopen access
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCCNE1 amplification
dc.subjectcyclin E1 expression
dc.subjecthigh-grade serous carcinoma
dc.subjectovarian cancer
dc.subjectprognosis
dc.titleCCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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