Exploring the link between MORF4L1 and risk of breast cancer

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Martrat, GriseldaIDIBELL,University Med Centre Utrecht (author)

Exploring the link between MORF4L1 and risk of breast cancer

Article/chapterEnglish2011

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2011-04-05
Springer Science and Business Media LLC,2011
electronicrdacarrier

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LIBRIS-ID:oai:lup.lub.lu.se:abfff1a4-5eb7-4fa1-bb7c-717d45d9b1fd
https://lup.lub.lu.se/record/2094273URI
https://doi.org/10.1186/bcr2862DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:122911763URI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156692URI
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-69933URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Rad51 Recombinase
RNA Interference
Nuclear Proteins
Mutation
Mice
Humans
Genetic Predisposition to Disease
BRCA2
BRCA1
Genes
Female
Fanconi Anemia Complementation Group D2 Protein
Fanconi Anemia
DNA Repair
DNA Damage
Cell Line
Caenorhabditis elegans
Animals
Breast Neoplasms
Replication Protein A
Risk Factors
Transcription Factors
Tumor Suppressor Proteins
Two-Hybrid System Techniques
MEDICINE
TECHNOLOGY

Added entries (persons, corporate bodies, meetings, titles ...)

Maxwell, Christopher A.IDIBELL (author)
Tominaga, EmikoUniversity of Texas Health Science Centre San Antonio (author)
Porta-de-la-Riva, MontserratChemoresistance and Predictive Factors of Tumor Response and Stromal Microenvironment, IDIBELL, Spain (author)
Bonifaci, NuriaIDIBELL (author)
Gomez-Baldo, LaiaIDIBELL (author)
Bogliolo, MassimoAutonomous University Barcelona (author)
Lazaro, ConxiIDIBELL (author)
Blanco, IgnacioIDIBELL (author)
Brunet, JoanHospital Josep Trueta (author)
Aguilar, HelenaBellvitge Institute Biomed Research IDIBELL (author)
Fernandez-Rodriguez, JuanaIDIBELL (author)
Seal, SheilaInstitute Canc Research (author)
Renwick, AnthonyInstitute Canc Research (author)
Rahman, NazneenInstitute Canc Research (author)
Kuehl, JuliaDepartment of Human Genetics, University of Würzburg, Biozentrum, Am Hubland, Würzburg, Germany (author)
Neveling, KorneliaUniversity Wurzburg (author)
Schindler, DetlevUniversity Wurzbur (author)
Ramirez, Maria J.Autonomous University Barcelona (author)
Castella, MariaAutonomous University Barcelon (author)
Hernandez, GonzaloAutonomous University Barcelona (author)
Easton, Douglas F.University Cambridge,Newcastle Upon Tyne Hospital NHS Trust (author)
Peock, SusanUniversity Cambridge (author)
Cook, MargaretUniversity Cambridge (author)
Oliver, Clare T.University Cambridge (author)
Frost, DebraUniversity Cambridge (author)
Platte, RadkaUniversity Cambridge (author)
Evans, D. GarethCent Manchester University Hospital NHS Fdn Trust (author)
Lalloo, FionaCent Manchester University Hospital NHS Fdn Trust (author)
Eeles, RosalindInstitute Canc Research, Oncogenet Team (author)
Izatt, LouiseGuys and St Thomas NHS Fdn Trust (author)
Chu, CarolSt James Hospital,University Cambridge (author)
Davidson, RosemarieFerguson Smith Centre Clin Genet (author)
Ong, Kai-RenBirmingham Womens Hospital Healthcare NHS Trust (author)
Cook, JackieSheffield Childrens Hospital (author)
Douglas, Fiona (author)
Hodgson, ShirleyUniversity London (author)
Brewer, CaroleRoyal Devon and Exeter Hospital (author)
Morrison, Patrick J.Belfast City Hospital (author)
Porteous, MaryWestern Gen Hospital (author)
Peterlongo, PaoloFdn IRCCS Ist Nazl Tumori INT,Leiden University (author)
Manoukian, SiranoushFdn IRCCS INT (author)
Peissel, BernardFdn IRCCS INT (author)
Zaffaroni, DanielaFdn IRCCS INT (author)
Roversi, GaiaFdn IRCCS INT (author)
Barile, MonicaIst Europeo Oncol IEO (author)
Viel, AlessandraIRCCS (author)
Pasini, BarbaraUniversity Turin (author)
Ottini, LauraUniversity Roma La Sapienza (author)
Putignano, Anna LauraFiorgen Fdn Pharmacogen (author)
Savarese, AntonellaRegina Elena Institute Canc Research (author)
Bernard, LorisIEO,Netherlands Canc Institute (author)
Radice, PaoloFdn IRCCS Ist Nazl Tumori INT (author)
Healey, SueQueensland Institute Med Research (author)
Spurdle, AmandaQueensland Institute Med Research (author)
Chen, XiaoqingQueensland Institute Med Research (author)
Beesley, JonathanQueensland Institute Med Research (author)
Rookus, Matti A.Netherlands Canc Institute (author)
Verhoef, SennoNetherlands Canc Institute (author)
Tilanus-Linthorst, Madeleine A.Erasmus MC Daniel den Hoed Canc Centre (author)
Vreeswijk, Maaike P. (author)
Asperen, Christi J.Leiden University (author)
Bodmer, DanielleRadboud University Nijmegen (author)
Ausems, Margreet G. E. M. (author)
van Os, Theo A.University Amsterdam (author)
Blok, Marinus J.University Hospital Maastricht (author)
Meijers-Heijboer, Hanne E. J.Vrije University Amsterdam Med Centre,Canc Prevent Institute Calif (author)
Hogervorst, Frans B. L. (author)
Goldgar, David E.University Utah (author)
Buys, SaundraHuntsman Canc Institute (author)
John, Esther M. (author)
Miron, AlexanderHarvard University (author)
Southey, MelissaUniversity Melbourne (author)
Daly, Mary B.Fox Chase Canc Centre (author)
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)
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)
Rantala, JohannaKarolinska Institutet,Karolinska University Hospital (author)
Barbany-Bustinza, GiselaKarolinska Institutet,Karolinska University Hospital (author)
Ehrencrona, HansUppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi(Swepub:lu)med-hen (author)
Stenmark Askmalm, MarieÖstergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik(Swepub:liu)marst93 (author)
Kaufman, BellaThe Institute of Oncology, Chaim Sheba Medical Center, Israel (author)
Laitman, YaelChaim Sheba Med Centre (author)
Milgrom, RoniChaim Sheba Med Centre (author)
Friedman, EitanChaim Sheba Med Centre (author)
Domchek, Susan M.University Penn (author)
Nathanson, Katherine L.University Penn (author)
Rebbeck, Timothy R.University Penn (author)
Johannsson, Oskar ThorDepartment of Oncology, 20A Landspitali-LSH v/Hringbraut, Reykjavik, Iceland (author)
Couch, Fergus J.Mayo Clin (author)
Wang, XianshuMayo Clin (author)
Fredericksen, ZacharyMayo Clin (author)
Cuadras, DanielIDIBELL (author)
Moreno, VctorIDIBELL (author)
Pientka, Friederike K.University Lubeck (author)
Depping, ReinhardUniversity Lubeck (author)
Caldes, TrinidadHospital Clin San Carlos (author)
Osorio, AnaSpanish Natl Canc Research Centre (author)
Benitez, JavierSpanish Natl Canc Research Centre (author)
Bueren, JuanCentre Invest Energet Medioambientales and Tecnol CIEM, (author)
Heikkinen, TuomasUniversity Helsinki (author)
Nevanlinna, HeliUniversity Helsinki (author)
Hamann, UteDeutsch Krebsforschungszentrum DKFZ (author)
Torres, DianaPontificia University Javeriana (author)
Caligo, Maria AdelaideUniversity Hospital Pisa (author)
Godwin, Andrew K.University Kansas (author)
Imyanitov, Evgeny N.NN Petrov Oncol Research Institute (author)
Janavicius, RamunasVilnius University Hospital (author)
Sinilnikova, Olga M.University Lyon 1 (author)
Stoppa-Lyonnet, DominiqueInstitute Curie (author)
Mazoyer, SylvieUniversity Lyon 1 (author)
Verny-Pierre, CaroleUniversity Lyon 1 (author)
Castera, LaurentInstitute Curie (author)
de Pauw, AntoineInstitute Curie (author)
Bignon, Yves-JeanUniversity Clermont Ferrand (author)
Uhrhammer, NancyUniversity Clermont Ferrand (author)
Peyrat, Jean-PhilippeCentre Oscar Lambret (author)
Vennin, PhilippeConsultation d'Oncogénétique, Centre Oscar Lambret, Lille, France (author)
Ferrer, Sandra FertHotel Dieu Centre Hospital (author)
Collonge-Rame, Marie-AgnesCHU Besancon (author)
Mortemousque, IsabelleCHU Bretonneau (author)
McGuffog, LesleyUniversity Cambridge (author)
Chenevix-Trench, GeorgiaQueensland Institute Med Research (author)
Pereira-Smith, Olivia M.University Texas Hlth Science Centre San Antonio (author)
Antoniou, Antonis C. (author)
Ceron, JulianIDIBELL (author)
Tominaga, KaoruUniversity Texas Hlth Science Centre San Antonio (author)
Surralles, JordiAutonomous University Barcelona (author)
Angel Pujana, MiguelCatalan Institute of Oncology, IDIBELL, Spain (author)
IDIBELLUniversity Med Centre Utrecht (creator_code:org_t)

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In:Breast Cancer Research: Springer Science and Business Media LLC13:21465-54111465-542X

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By the author/editor: Martrat, Griseld ...; Maxwell, Christo ...; Tominaga, Emiko; Porta-de-la-Riva ...; Bonifaci, Nuria; Gomez-Baldo, Lai ...; show more...; Bogliolo, Massim ...; Lazaro, Conxi; Blanco, Ignacio; Brunet, Joan; Aguilar, Helena; Fernandez-Rodrig ...; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Kuehl, Julia; Neveling, Kornel ...; Schindler, Detle ...; Ramirez, Maria J ...; Castella, Maria; Hernandez, Gonza ...; Easton, Douglas ...; Peock, Susan; Cook, Margaret; Oliver, Clare T.; Frost, Debra; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Rosalind; Izatt, Louise; Chu, Carol; Davidson, Rosema ...; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Brewer, Carole; Morrison, Patric ...; Porteous, Mary; Peterlongo, Paol ...; Manoukian, Siran ...; Peissel, Bernard; Zaffaroni, Danie ...; Roversi, Gaia; Barile, Monica; Viel, Alessandra; Pasini, Barbara; Ottini, Laura; Putignano, Anna ...; Savarese, Antone ...; Bernard, Loris; Radice, Paolo; Healey, Sue; Spurdle, Amanda; Chen, Xiaoqing; Beesley, Jonatha ...; Rookus, Matti A.; Verhoef, Senno; Tilanus-Linthors ...; Vreeswijk, Maaik ...; Asperen, Christi ...; Bodmer, Danielle; Ausems, Margreet ...; van Os, Theo A.; Blok, Marinus J.; Meijers-Heijboer ...; Hogervorst, Fran ...; Goldgar, David E ...; Buys, Saundra; John, Esther M.; Miron, Alexander; Southey, Melissa; Daly, Mary B.; Harbst, Katja; Borg, Åke; Rantala, Johanna; Barbany-Bustinza ...; Ehrencrona, Hans; Stenmark Askmalm ...; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Friedman, Eitan; Domchek, Susan M ...; Nathanson, Kathe ...; Rebbeck, Timothy ...; Johannsson, Oska ...; Couch, Fergus J.; Wang, Xianshu; Fredericksen, Za ...; Cuadras, Daniel; Moreno, Vctor; Pientka, Frieder ...; Depping, Reinhar ...; Caldes, Trinidad; Osorio, Ana; Benitez, Javier; Bueren, Juan; Heikkinen, Tuoma ...; Nevanlinna, Heli; Hamann, Ute; Torres, Diana; Caligo, Maria Ad ...; Godwin, Andrew K ...; Imyanitov, Evgen ...; Janavicius, Ramu ...; Sinilnikova, Olg ...; Stoppa-Lyonnet, ...; Mazoyer, Sylvie; Verny-Pierre, Ca ...; Castera, Laurent; de Pauw, Antoine; Bignon, Yves-Jea ...; Uhrhammer, Nancy; Peyrat, Jean-Phi ...; Vennin, Philippe; Ferrer, Sandra F ...; Collonge-Rame, M ...; Mortemousque, Is ...; McGuffog, Lesley; Chenevix-Trench, ...; Pereira-Smith, O ...; Antoniou, Antoni ...; Ceron, Julian; Tominaga, Kaoru; Surralles, Jordi; Angel Pujana, Mi ...; show less...

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