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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
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.authorVijver, Koen K.
dc.contributor.authorAa, Maaike A.
dc.contributor.authorGorp, Toon
dc.contributor.authorNieuwenhuysen, 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.date.accessioned2023-03-03T21:08:50Z
dc.date.available2024-04-03 16:08:48en
dc.date.available2023-03-03T21:08:50Z
dc.date.issued2023-03-01
dc.identifier.citationKang, Eun-Young ; Weir, Ashley; Meagher, Nicola S.; Farrington, Kyo; Nelson, Gregg S.; Ghatage, Prafull; Lee, Cheng-Han ; Riggan, Marjorie J.; Bolithon, Adelyn; Popovic, Gordana; Leung, Betty; Tang, Katrina; Lambie, Neil; Millstein, Joshua; Alsop, Jennifer; Anglesio, Michael S.; Ataseven, Beyhan; Barlow, Ellen; Beckmann, Matthias W.; Berger, Jessica; Bisinotto, Christiani; Bösmüller, Hans ; Boros, Jessica; Brand, Alison H.; Brooks-Wilson, Angela ; Brucker, Sara Y.; Carney, Michael E.; Casablanca, Yovanni; Cazorla-Jiménez, Alicia ; Cohen, Paul A.; Conrads, Thomas P.; Cook, Linda S.; Coulson, Penny; Courtney-Brooks, Madeleine ; Cramer, Daniel W.; Crowe, Philip; Cunningham, Julie M.; Cybulski, Cezary; Darcy, Kathleen M.; El-Bahrawy, Mona A. ; Elishaev, Esther; Erber, Ramona; Farrell, Rhonda; Fereday, Sian; Fischer, Anna; García, María J. ; Gayther, Simon A.; Gentry-Maharaj, Aleksandra ; Gilks, C. Blake; Grube, Marcel; Harnett, Paul R.; Harrington, Shariska Petersen; Harter, Philipp; Hartmann, Arndt; Hecht, Jonathan L.; Heikaus, Sebastian; Hein, Alexander; Heitz, Florian; Hendley, Joy; Hernandez, Brenda Y.; Polo, Susanna Hernando; Heublein, Sabine; Hirasawa, Akira; Høgdall, Estrid ; Høgdall, Claus K. ; Horlings, Hugo M.; Huntsman, David G.; Huzarski, Tomasz; Jewell, Andrea; Jimenez-Linan, Mercedes ; Jones, Michael E.; Kaufmann, Scott H.; Kennedy, Catherine J.; Khabele, Dineo; Kommoss, Felix K. F.; Kruitwagen, Roy F. P. M.; Lambrechts, Diether; Le, Nhu D.; Lener, Marcin; Lester, Jenny; Leung, Yee; Linder, Anna; Loverix, Liselore; Lubiński, Jan ; Madan, Rashna; Maxwell, G. Larry; Modugno, Francesmary; Neuhausen, Susan L.; Olawaiye, Alexander; Olbrecht, Siel; Orsulic, Sandra; Palacios, José ; Pearce, Celeste Leigh; Pike, Malcolm C.; Quinn, Carmel M.; Mohan, Ganendra Raj; Rodríguez-Antona, Cristina ; Ruebner, Matthias; Ryan, Andy; Salfinger, Stuart G.; Sasamoto, Naoko; Schildkraut, Joellen M.; Schoemaker, Minouk J.; Shah, Mitul; Sharma, Raghwa; Shvetsov, Yurii B.; Singh, Naveena; Sonke, Gabe S.; Steele, Linda; Stewart, Colin J. R.; Sundfeldt, Karin; Swerdlow, Anthony J.; Talhouk, Aline; Tan, Adeline; Taylor, Sarah E.; Terry, Kathryn L.; Tołoczko, Aleksandra ; Traficante, Nadia; Vijver, Koen K.; Aa, Maaike A.; Gorp, Toon; Nieuwenhuysen, Els; Van-Wagensveld, Lilian ; Vergote, Ignace; Vierkant, Robert A.; Wang, Chen; Wilkens, Lynne R.; Winham, Stacey J.; Wu, Anna H.; Benitez, Javier; Berchuck, Andrew; Candido dos Reis, Francisco J.; DeFazio, Anna; Fasching, Peter A.; Goode, Ellen L.; Goodman, Marc T.; Gronwald, Jacek; Karlan, Beth Y.; Kommoss, Stefan; Menon, Usha; Sinn, Hans-Peter ; Staebler, Annette; Brenton, James D.; Bowtell, David D.; Pharoah, Paul D. P.; Ramus, Susan J.; Köbel, Martin (2023). "CCNE1 and survival of patients with tubo- ovarian high- grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study." Cancer 129(5): 697-713.
dc.identifier.issn0008-543X
dc.identifier.issn1097-0142
dc.identifier.urihttps://hdl.handle.net/2027.42/175893
dc.description.abstractBackgroundCyclin 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.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-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.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.Multi-institutional validation of the prognostic value of cyclin E1 high-level amplification and overexpression in 3029 tubo-ovarian high-grade serous carcinoma cases support its value as a prognostic biomarker in this disease.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherprognosis
dc.subject.otherovarian cancer
dc.subject.otherhigh-grade serous carcinoma
dc.subject.othercyclin E1 expression
dc.subject.otherCCNE1 amplification
dc.titleCCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelPublic Health
dc.subject.hlbsecondlevelOncology and Hematology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175893/1/cncr34582.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175893/2/cncr34582-sup-0001-suppl-data.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175893/3/cncr34582_am.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175893/4/cncr34582-sup-0003-table_s1.pdf
dc.identifier.doi10.1002/cncr.34582
dc.identifier.sourceCancer
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dc.working.doiNOen
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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