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Exploring the link ...
Exploring the link between MORF4L1 and risk of breast cancer
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- Martrat, Griselda (author)
- IDIBELL,University Med Centre Utrecht
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- Maxwell, Christopher A. (author)
- IDIBELL
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- Tominaga, Emiko (author)
- University of Texas Health Science Centre San Antonio
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show more...
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- Porta-de-la-Riva, Montserrat (author)
- Chemoresistance and Predictive Factors of Tumor Response and Stromal Microenvironment, IDIBELL, Spain
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- Bonifaci, Nuria (author)
- IDIBELL
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- Gomez-Baldo, Laia (author)
- IDIBELL
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- Bogliolo, Massimo (author)
- Autonomous University Barcelona
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- Lazaro, Conxi (author)
- IDIBELL
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- Blanco, Ignacio (author)
- IDIBELL
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- Brunet, Joan (author)
- Hospital Josep Trueta
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- Aguilar, Helena (author)
- Bellvitge Institute Biomed Research IDIBELL
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- Fernandez-Rodriguez, Juana (author)
- IDIBELL
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- Seal, Sheila (author)
- Institute Canc Research
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- Renwick, Anthony (author)
- Institute Canc Research
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- Rahman, Nazneen (author)
- Institute Canc Research
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- Kuehl, Julia (author)
- Department of Human Genetics, University of Würzburg, Biozentrum, Am Hubland, Würzburg, Germany
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- Neveling, Kornelia (author)
- University Wurzburg
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- Schindler, Detlev (author)
- University Wurzbur
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- Ramirez, Maria J. (author)
- Autonomous University Barcelona
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- Castella, Maria (author)
- Autonomous University Barcelon
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- Hernandez, Gonzalo (author)
- Autonomous University Barcelona
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- Easton, Douglas F. (author)
- University Cambridge,Newcastle Upon Tyne Hospital NHS Trust
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- Peock, Susan (author)
- University Cambridge
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- Cook, Margaret (author)
- University Cambridge
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- Oliver, Clare T. (author)
- University Cambridge
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- Frost, Debra (author)
- University Cambridge
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- Platte, Radka (author)
- University Cambridge
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- Evans, D. Gareth (author)
- Cent Manchester University Hospital NHS Fdn Trust
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- Lalloo, Fiona (author)
- Cent Manchester University Hospital NHS Fdn Trust
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- Eeles, Rosalind (author)
- Institute Canc Research, Oncogenet Team
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- Izatt, Louise (author)
- Guys and St Thomas NHS Fdn Trust
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- Chu, Carol (author)
- St James Hospital,University Cambridge
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- Davidson, Rosemarie (author)
- Ferguson Smith Centre Clin Genet
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- Ong, Kai-Ren (author)
- Birmingham Womens Hospital Healthcare NHS Trust
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- Cook, Jackie (author)
- Sheffield Childrens Hospital
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Douglas, Fiona (author)
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- Hodgson, Shirley (author)
- University London
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- Brewer, Carole (author)
- Royal Devon and Exeter Hospital
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- Morrison, Patrick J. (author)
- Belfast City Hospital
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- Porteous, Mary (author)
- Western Gen Hospital
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- Peterlongo, Paolo (author)
- Fdn IRCCS Ist Nazl Tumori INT,Leiden University
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- Manoukian, Siranoush (author)
- Fdn IRCCS INT
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- Peissel, Bernard (author)
- Fdn IRCCS INT
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- Zaffaroni, Daniela (author)
- Fdn IRCCS INT
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- Roversi, Gaia (author)
- Fdn IRCCS INT
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- Barile, Monica (author)
- Ist Europeo Oncol IEO
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- Viel, Alessandra (author)
- IRCCS
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- Pasini, Barbara (author)
- University Turin
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- Ottini, Laura (author)
- University Roma La Sapienza
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- Putignano, Anna Laura (author)
- Fiorgen Fdn Pharmacogen
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- Savarese, Antonella (author)
- Regina Elena Institute Canc Research
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- Bernard, Loris (author)
- IEO,Netherlands Canc Institute
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- Radice, Paolo (author)
- Fdn IRCCS Ist Nazl Tumori INT
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- Healey, Sue (author)
- Queensland Institute Med Research
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- Spurdle, Amanda (author)
- Queensland Institute Med Research
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- Chen, Xiaoqing (author)
- Queensland Institute Med Research
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- Beesley, Jonathan (author)
- Queensland Institute Med Research
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- Rookus, Matti A. (author)
- Netherlands Canc Institute
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- Verhoef, Senno (author)
- Netherlands Canc Institute
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- Tilanus-Linthorst, Madeleine A. (author)
- Erasmus MC Daniel den Hoed Canc Centre
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Vreeswijk, Maaike P. (author)
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- Asperen, Christi J. (author)
- Leiden University
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- Bodmer, Danielle (author)
- Radboud University Nijmegen
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Ausems, Margreet G. E. M. (author)
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- van Os, Theo A. (author)
- University Amsterdam
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- Blok, Marinus J. (author)
- University Hospital Maastricht
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- Meijers-Heijboer, Hanne E. J. (author)
- 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. (author)
- University Utah
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- Buys, Saundra (author)
- Huntsman Canc Institute
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John, Esther M. (author)
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- Miron, Alexander (author)
- Harvard University
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- Southey, Melissa (author)
- University Melbourne
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- Daly, Mary B. (author)
- Fox Chase Canc Centre
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- Harbst, Katja (author)
- Lund 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
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- Borg, Åke (author)
- Lund 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
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- Rantala, Johanna (author)
- Karolinska Institutet,Karolinska University Hospital
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- Barbany-Bustinza, Gisela (author)
- Karolinska Institutet,Karolinska University Hospital
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- Ehrencrona, Hans (author)
- Uppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi
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- Stenmark Askmalm, Marie (author)
- Östergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik
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- Kaufman, Bella (author)
- The Institute of Oncology, Chaim Sheba Medical Center, Israel
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- Laitman, Yael (author)
- Chaim Sheba Med Centre
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- Milgrom, Roni (author)
- Chaim Sheba Med Centre
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- Friedman, Eitan (author)
- Chaim Sheba Med Centre
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- Domchek, Susan M. (author)
- University Penn
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- Nathanson, Katherine L. (author)
- University Penn
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- Rebbeck, Timothy R. (author)
- University Penn
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- Johannsson, Oskar Thor (author)
- Department of Oncology, 20A Landspitali-LSH v/Hringbraut, Reykjavik, Iceland
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- Couch, Fergus J. (author)
- Mayo Clin
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- Wang, Xianshu (author)
- Mayo Clin
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- Fredericksen, Zachary (author)
- Mayo Clin
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- Cuadras, Daniel (author)
- IDIBELL
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- Moreno, Vctor (author)
- IDIBELL
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- Pientka, Friederike K. (author)
- University Lubeck
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- Depping, Reinhard (author)
- University Lubeck
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- Caldes, Trinidad (author)
- Hospital Clin San Carlos
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- Osorio, Ana (author)
- Spanish Natl Canc Research Centre
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- Benitez, Javier (author)
- Spanish Natl Canc Research Centre
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- Bueren, Juan (author)
- Centre Invest Energet Medioambientales and Tecnol CIEM,
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- Heikkinen, Tuomas (author)
- University Helsinki
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- Nevanlinna, Heli (author)
- University Helsinki
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- Hamann, Ute (author)
- Deutsch Krebsforschungszentrum DKFZ
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- Torres, Diana (author)
- Pontificia University Javeriana
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- Caligo, Maria Adelaide (author)
- University Hospital Pisa
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- Godwin, Andrew K. (author)
- University Kansas
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- Imyanitov, Evgeny N. (author)
- NN Petrov Oncol Research Institute
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- Janavicius, Ramunas (author)
- Vilnius University Hospital
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- Sinilnikova, Olga M. (author)
- University Lyon 1
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- Stoppa-Lyonnet, Dominique (author)
- Institute Curie
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- Mazoyer, Sylvie (author)
- University Lyon 1
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- Verny-Pierre, Carole (author)
- University Lyon 1
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- Castera, Laurent (author)
- Institute Curie
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- de Pauw, Antoine (author)
- Institute Curie
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- Bignon, Yves-Jean (author)
- University Clermont Ferrand
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- Uhrhammer, Nancy (author)
- University Clermont Ferrand
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- Peyrat, Jean-Philippe (author)
- Centre Oscar Lambret
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- Vennin, Philippe (author)
- Consultation d'Oncogénétique, Centre Oscar Lambret, Lille, France
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- Ferrer, Sandra Fert (author)
- Hotel Dieu Centre Hospital
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- Collonge-Rame, Marie-Agnes (author)
- CHU Besancon
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- Mortemousque, Isabelle (author)
- CHU Bretonneau
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- McGuffog, Lesley (author)
- University Cambridge
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- Chenevix-Trench, Georgia (author)
- Queensland Institute Med Research
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- Pereira-Smith, Olivia M. (author)
- University Texas Hlth Science Centre San Antonio
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Antoniou, Antonis C. (author)
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- Ceron, Julian (author)
- IDIBELL
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- Tominaga, Kaoru (author)
- University Texas Hlth Science Centre San Antonio
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- Surralles, Jordi (author)
- Autonomous University Barcelona
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- Angel Pujana, Miguel (author)
- Catalan Institute of Oncology, IDIBELL, Spain
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(creator_code:org_t)
- 2011-04-05
- 2011
- English.
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
- Related links:
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http://dx.doi.org/10... (free)
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10... (free)
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https://breast-cance...
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https://liu.diva-por... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- 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
Publication and Content Type
- art (subject category)
- ref (subject category)
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van Os, Theo A.
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Hogervorst, Fran ...
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Buys, Saundra
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John, Esther M.
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Miron, Alexander
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Southey, Melissa
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Daly, Mary B.
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Harbst, Katja
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Borg, Åke
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Rantala, Johanna
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Barbany-Bustinza ...
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Ehrencrona, Hans
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Stenmark Askmalm ...
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Johannsson, Oska ...
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Couch, Fergus J.
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Moreno, Vctor
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Pientka, Frieder ...
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Caldes, Trinidad
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Osorio, Ana
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Benitez, Javier
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Heikkinen, Tuoma ...
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Nevanlinna, Heli
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Hamann, Ute
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Torres, Diana
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Caligo, Maria Ad ...
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Godwin, Andrew K ...
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Imyanitov, Evgen ...
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Janavicius, Ramu ...
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Sinilnikova, Olg ...
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Stoppa-Lyonnet, ...
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Mazoyer, Sylvie
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Verny-Pierre, Ca ...
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Castera, Laurent
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de Pauw, Antoine
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Uhrhammer, Nancy
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Peyrat, Jean-Phi ...
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Vennin, Philippe
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Ferrer, Sandra F ...
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Collonge-Rame, M ...
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Mortemousque, Is ...
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McGuffog, Lesley
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Chenevix-Trench, ...
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Pereira-Smith, O ...
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Antoniou, Antoni ...
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Ceron, Julian
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Tominaga, Kaoru
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Surralles, Jordi
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Angel Pujana, Mi ...
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- MEDICAL AND HEALTH SCIENCES
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Breast Cancer Re ...
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Lund University
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Karolinska Institutet
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Uppsala University
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Linköping University