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Exploring the link ...
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Martrat, GriseldaIDIBELL,University Med Centre Utrecht
(author)
Exploring the link between MORF4L1 and risk of breast cancer
- Article/chapterEnglish2011
Publisher, publication year, extent ...
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2011-04-05
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Springer Science and Business Media LLC,2011
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:abfff1a4-5eb7-4fa1-bb7c-717d45d9b1fd
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https://lup.lub.lu.se/record/2094273URI
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https://doi.org/10.1186/bcr2862DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:122911763URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156692URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-69933URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Maxwell, Christopher A.IDIBELL
(author)
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Tominaga, EmikoUniversity of Texas Health Science Centre San Antonio
(author)
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Porta-de-la-Riva, MontserratChemoresistance and Predictive Factors of Tumor Response and Stromal Microenvironment, IDIBELL, Spain
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Bonifaci, NuriaIDIBELL
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Gomez-Baldo, LaiaIDIBELL
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Bogliolo, MassimoAutonomous University Barcelona
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Lazaro, ConxiIDIBELL
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Blanco, IgnacioIDIBELL
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Brunet, JoanHospital Josep Trueta
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Aguilar, HelenaBellvitge Institute Biomed Research IDIBELL
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Fernandez-Rodriguez, JuanaIDIBELL
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Seal, SheilaInstitute Canc Research
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Renwick, AnthonyInstitute Canc Research
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Rahman, NazneenInstitute Canc Research
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Kuehl, JuliaDepartment of Human Genetics, University of Würzburg, Biozentrum, Am Hubland, Würzburg, Germany
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Neveling, KorneliaUniversity Wurzburg
(author)
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Schindler, DetlevUniversity Wurzbur
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Ramirez, Maria J.Autonomous University Barcelona
(author)
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Castella, MariaAutonomous University Barcelon
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Hernandez, GonzaloAutonomous University Barcelona
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Easton, Douglas F.University Cambridge,Newcastle Upon Tyne Hospital NHS Trust
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Peock, SusanUniversity Cambridge
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Cook, MargaretUniversity Cambridge
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Oliver, Clare T.University Cambridge
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Frost, DebraUniversity Cambridge
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Platte, RadkaUniversity Cambridge
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Evans, D. GarethCent Manchester University Hospital NHS Fdn Trust
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Lalloo, FionaCent Manchester University Hospital NHS Fdn Trust
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Eeles, RosalindInstitute Canc Research, Oncogenet Team
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Izatt, LouiseGuys and St Thomas NHS Fdn Trust
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Chu, CarolSt James Hospital,University Cambridge
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Davidson, RosemarieFerguson Smith Centre Clin Genet
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Ong, Kai-RenBirmingham Womens Hospital Healthcare NHS Trust
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Cook, JackieSheffield Childrens Hospital
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Douglas, Fiona
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Hodgson, ShirleyUniversity London
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Brewer, CaroleRoyal Devon and Exeter Hospital
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Morrison, Patrick J.Belfast City Hospital
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Porteous, MaryWestern Gen Hospital
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Peterlongo, PaoloFdn IRCCS Ist Nazl Tumori INT,Leiden University
(author)
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Manoukian, SiranoushFdn IRCCS INT
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Peissel, BernardFdn IRCCS INT
(author)
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Zaffaroni, DanielaFdn IRCCS INT
(author)
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Roversi, GaiaFdn IRCCS INT
(author)
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Barile, MonicaIst Europeo Oncol IEO
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Viel, AlessandraIRCCS
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Pasini, BarbaraUniversity Turin
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Ottini, LauraUniversity Roma La Sapienza
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Putignano, Anna LauraFiorgen Fdn Pharmacogen
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Savarese, AntonellaRegina Elena Institute Canc Research
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Bernard, LorisIEO,Netherlands Canc Institute
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Radice, PaoloFdn IRCCS Ist Nazl Tumori INT
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Healey, SueQueensland Institute Med Research
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Spurdle, AmandaQueensland Institute Med Research
(author)
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Chen, XiaoqingQueensland Institute Med Research
(author)
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Beesley, JonathanQueensland Institute Med Research
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Rookus, Matti A.Netherlands Canc Institute
(author)
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Verhoef, SennoNetherlands Canc Institute
(author)
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Tilanus-Linthorst, Madeleine A.Erasmus MC Daniel den Hoed Canc Centre
(author)
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Vreeswijk, Maaike P.
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Asperen, Christi J.Leiden University
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Bodmer, DanielleRadboud University Nijmegen
(author)
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Ausems, Margreet G. E. M.
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van Os, Theo A.University Amsterdam
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Blok, Marinus J.University Hospital Maastricht
(author)
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Meijers-Heijboer, Hanne E. J.Vrije University Amsterdam Med Centre,Canc Prevent Institute Calif
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Hogervorst, Frans B. L.
(author)
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Goldgar, David E.University Utah
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Buys, SaundraHuntsman Canc Institute
(author)
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John, Esther M.
(author)
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Miron, AlexanderHarvard University
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Southey, MelissaUniversity Melbourne
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Daly, Mary B.Fox Chase Canc Centre
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Harbst, KatjaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skane University Hospital(Swepub:lu)med-kbn
(author)
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Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skane University Hospital(Swepub:lu)onk-abo
(author)
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Rantala, JohannaKarolinska Institutet,Karolinska University Hospital
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Barbany-Bustinza, GiselaKarolinska Institutet,Karolinska University Hospital
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Ehrencrona, HansUppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi(Swepub:lu)med-hen
(author)
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Stenmark Askmalm, MarieÖstergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik(Swepub:liu)marst93
(author)
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Kaufman, BellaThe Institute of Oncology, Chaim Sheba Medical Center, Israel
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Laitman, YaelChaim Sheba Med Centre
(author)
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Milgrom, RoniChaim Sheba Med Centre
(author)
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Friedman, EitanChaim Sheba Med Centre
(author)
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Domchek, Susan M.University Penn
(author)
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Nathanson, Katherine L.University Penn
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Rebbeck, Timothy R.University Penn
(author)
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Johannsson, Oskar ThorDepartment of Oncology, 20A Landspitali-LSH v/Hringbraut, Reykjavik, Iceland
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Couch, Fergus J.Mayo Clin
(author)
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Wang, XianshuMayo Clin
(author)
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Fredericksen, ZacharyMayo Clin
(author)
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Cuadras, DanielIDIBELL
(author)
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Moreno, VctorIDIBELL
(author)
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Pientka, Friederike K.University Lubeck
(author)
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Depping, ReinhardUniversity Lubeck
(author)
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Caldes, TrinidadHospital Clin San Carlos
(author)
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Osorio, AnaSpanish Natl Canc Research Centre
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Benitez, JavierSpanish Natl Canc Research Centre
(author)
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Bueren, JuanCentre Invest Energet Medioambientales and Tecnol CIEM,
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Heikkinen, TuomasUniversity Helsinki
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Nevanlinna, HeliUniversity Helsinki
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Hamann, UteDeutsch Krebsforschungszentrum DKFZ
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Torres, DianaPontificia University Javeriana
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Caligo, Maria AdelaideUniversity Hospital Pisa
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Godwin, Andrew K.University Kansas
(author)
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Imyanitov, Evgeny N.NN Petrov Oncol Research Institute
(author)
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Janavicius, RamunasVilnius University Hospital
(author)
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Sinilnikova, Olga M.University Lyon 1
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Stoppa-Lyonnet, DominiqueInstitute Curie
(author)
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Mazoyer, SylvieUniversity Lyon 1
(author)
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Verny-Pierre, CaroleUniversity Lyon 1
(author)
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Castera, LaurentInstitute Curie
(author)
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de Pauw, AntoineInstitute Curie
(author)
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Bignon, Yves-JeanUniversity Clermont Ferrand
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Uhrhammer, NancyUniversity Clermont Ferrand
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Peyrat, Jean-PhilippeCentre Oscar Lambret
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Vennin, PhilippeConsultation d'Oncogénétique, Centre Oscar Lambret, Lille, France
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Ferrer, Sandra FertHotel Dieu Centre Hospital
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Collonge-Rame, Marie-AgnesCHU Besancon
(author)
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Mortemousque, IsabelleCHU Bretonneau
(author)
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McGuffog, LesleyUniversity Cambridge
(author)
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Chenevix-Trench, GeorgiaQueensland Institute Med Research
(author)
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Pereira-Smith, Olivia M.University Texas Hlth Science Centre San Antonio
(author)
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Antoniou, Antonis C.
(author)
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Ceron, JulianIDIBELL
(author)
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Tominaga, KaoruUniversity Texas Hlth Science Centre San Antonio
(author)
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Surralles, JordiAutonomous University Barcelona
(author)
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Angel Pujana, MiguelCatalan Institute of Oncology, IDIBELL, Spain
(author)
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IDIBELLUniversity Med Centre Utrecht
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In:Breast Cancer Research: Springer Science and Business Media LLC13:21465-54111465-542X
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