Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer


Por: Maxwell, CA, Benitez, J, Gomez-Baldo, L, Osorio, A, Bonifaci, N, Fernandez-Ramires, R, Costes, SV, Guino, E, Chen, H, Evans, GJR, Mohan, P, Catala, I, Petit, A, Aguilar, H, Villanueva, A, Aytes, A, Serra-Musach, J, Rennert, G, Lejbkowicz, F, Peterlongo, P, Manoukian, S, Peissel, B, Ripamonti, CB, Bonanni, B, Viel, A, Allavena, A, Bernard, L, Radice, P, Friedman, E, Kaufman, B, Laitman, Y, Dubrovsky, M, Milgrom, R, Jakubowska, A, Cybulski, C, Gorski, B, Jaworska, K, Durda, K, Sukiennicki, G, Lubinski, J, Shugart, YY, Domchek, SM, Letrero, R, Weber, BL, Hogervorst, FBL, Rookus, MA, Collee, JM, Devilee, P, Ligtenberg, MJ, van der Luijt, RB, Aalfs, CM, Waisfisz, Q, Wijnen, J, van Roozendaal, CEP, Easton, DF, Peock, S, Cook, M, Oliver, C, Frost, D, Harrington, P, Evans, DG, Lalloo, F, Eeles, R, Izatt, L, Chu, C, Eccles, D, Douglas, F, Brewer, C, Nevanlinna, H, Heikkinen, T, Couch, FJ, Lindor, NM, Wang, XS, Godwin, AK, Caligo, MA, Lombardi, G, Loman, N, Karlsson, P, Ehrencrona, H, von Wachenfeldt, A, Barkardottir, RB, Hamann, U, Rashid, MU, Lasa, A, Caldes, T, Andres, R, Schmitt, M, Assmann, V, Stevens, K, Offit, K, Curado, J, Tilgner, H, Guigo, R, Aiza, G, Brunet, J, Castellsague, J, Martrat, G, Urruticoechea, A, Blanco, I, Tihomirova, L, Goldgar, DE, Buys, S, John, EM, Miron, A, Southey, M, Daly, MB, Schmutzler, RK, Wappenschmidt, B, Meindl, A, Arnold, N, Deissler, H, Varon-Mateeva, R, Sutter, C, Niederacher, D, Imyamitov, E, Sinilnikova, OM, Stoppa-Lyonne, D, Mazoyer, S, Verny-Pierre, C, Castera, L, de Pauw, A, Bignon, YJ, Uhrhammer, N, Peyrat, JP, Vennin, P, Ferrer, SF, Collonge-Rame, MA, Mortemousque, I, Spurdle, AB, Beesley, J, Chen, XQ, Healey, S, Barcellos-Hoff, MH, Vidal, M, Gruber, SB, Lazaro, C, Capella, G, McGuffog, L, Nathanson, KL, Antoniou, AC, Chenevix-Trench, G, Fleisch, MC, Moreno, V, Pujana, MA
Publicada: 1 nov 2011
Resumen:
Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (wHR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
Filiaciones:
Maxwell, CA:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Benitez, J:
 Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain
Gomez-Baldo, L:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Osorio, A:
 Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain
Bonifaci, N:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Biomarkers & Susceptibil Unit, Lhospitalet De Llobregat, Catalonia, Spain
Fernandez-Ramires, R:
 Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain
Costes, SV:
 Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
Guino, E:
 IDIBELL, Catalan Inst Oncol, Biomarkers & Susceptibil Unit, Lhospitalet De Llobregat, Catalonia, Spain
Catala, I:
 Univ Hosp Bellvitge, IDIBELL, Dept Pathol, Lhospitalet De Llobregat, Catalonia, Spain
Petit, A:
 Univ Hosp Bellvitge, IDIBELL, Dept Pathol, Lhospitalet De Llobregat, Catalonia, Spain
Aguilar, H:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Villanueva, A:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Aytes, A:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Serra-Musach, J:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Biomarkers & Susceptibil Unit, Lhospitalet De Llobregat, Catalonia, Spain
Rennert, G:
 Technion Israel Inst Technol, Carmel Med Ctr, Dept Community Med & Epidemiol, CHS Natl Canc Control Ctr, Haifa, Israel

 Technion Israel Inst Technol, B Rappaport Fac Med, Haifa, Israel
Lejbkowicz, F:
 Technion Israel Inst Technol, Carmel Med Ctr, Dept Community Med & Epidemiol, CHS Natl Canc Control Ctr, Haifa, Israel

 Technion Israel Inst Technol, B Rappaport Fac Med, Haifa, Israel
Peterlongo, P:
 Fdn IRCCS, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Ist Nazl Tumori, Milan, Italy

 IFOM Fdn, Ist FIRC Oncol Mol, Milan, Italy
Manoukian, S:
 Fdn IRCCS, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy
Peissel, B:
 Fdn IRCCS, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy
Ripamonti, CB:
 Fdn IRCCS, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Ist Nazl Tumori, Milan, Italy

 IFOM Fdn, Ist FIRC Oncol Mol, Milan, Italy

 Fdn IRCCS, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy
Bonanni, B:
 Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy
Viel, A:
 IRCCS, Ctr Riferimento Oncol, Div Expt Oncol 1, Aviano, Italy
Allavena, A:
 Univ Turin, Dept Genet Biol & Biochem, Turin, Italy
Bernard, L:
 Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy

 Consortium Genom Technol Cogentech, Milan, Italy
Radice, P:
 Fdn IRCCS, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Ist Nazl Tumori, Milan, Italy

 IFOM Fdn, Ist FIRC Oncol Mol, Milan, Italy
Friedman, E:
 Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, Ramat Gan, Israel

 Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel
Kaufman, B:
 Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, Ramat Gan, Israel
Laitman, Y:
 Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, Ramat Gan, Israel
Dubrovsky, M:
 Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, Ramat Gan, Israel
Milgrom, R:
 Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, Ramat Gan, Israel
Jakubowska, A:
 Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Cybulski, C:
 Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Gorski, B:
 Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Jaworska, K:
 Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Durda, K:
 Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Sukiennicki, G:
 Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Lubinski, J:
 Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland
Shugart, YY:
 NIMH, Unit Stat Genet, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA
Domchek, SM:
 Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Letrero, R:
 Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Weber, BL:
 Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Hogervorst, FBL:
 Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands
Rookus, MA:
 Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands
Collee, JM:
 Erasmus Univ, Dept Clin Genet, Med Ctr, Rotterdam Family Canc Clin, NL-3000 DR Rotterdam, Netherlands
Devilee, P:
 Leiden Univ, Dept Genet Epidemiol, Med Ctr, Leiden, Netherlands
Ligtenberg, MJ:
 Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands
van der Luijt, RB:
 Univ Utrecht, Med Ctr, Dept Clin Mol Genet, Utrecht, Netherlands
Aalfs, CM:
 Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
Waisfisz, Q:
 Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands
Wijnen, J:
 Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands
van Roozendaal, CEP:
 Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands
Easton, DF:
 Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Peock, S:
 Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Cook, M:
 Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Oliver, C:
 Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Frost, D:
 Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Harrington, P:
 Univ Cambridge, Dept Oncol, Cambridge, England
Evans, DG:
 Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England
Lalloo, F:
 Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England
Eeles, R:
 Royal Marsden NHS Fdn Trust, Sutton, Surrey, England
Izatt, L:
 Guys & St Thomas NHS Fdn Trust, London, England
Chu, C:
 St James Hosp, Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England
Eccles, D:
 Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England
Douglas, F:
 Newcastle Upon Tyne Hosp NHS Trust, Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England
Brewer, C:
 Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England
Nevanlinna, H:
 Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland
Heikkinen, T:
 Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland
Couch, FJ:
 Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA
Lindor, NM:
 Mayo Clin, Dept Med Genet, Rochester, MN USA
Wang, XS:
 Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA
Godwin, AK:
 Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA
Caligo, MA:
 Univ Pisa, Sect Genet Oncol, Dept Oncol, Pisa, Italy

 Univ Hosp Pisa, Dept Lab Med, Pisa, Italy
Lombardi, G:
 Univ Pisa, Sect Genet Oncol, Dept Oncol, Pisa, Italy

 Univ Hosp Pisa, Dept Lab Med, Pisa, Italy
Loman, N:
 Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden
Karlsson, P:
 Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden
Ehrencrona, H:
 Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden
von Wachenfeldt, A:
 Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
Barkardottir, RB:
 Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland
Hamann, U:
 Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany
Rashid, MU:
 Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany

 Shaukat Khanum Mem Canc Hosp & Res Ctr, Dept Basic Sci, Lahore, Pakistan
Lasa, A:
 Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Catalonia, Spain
Caldes, T:
 Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain
Andres, R:
 Hosp Clin Zaragoza, Div Med Oncol, Zaragoza, Spain
Schmitt, M:
 Univ Rostock, Dept Internal Med 3, Rostock, Germany
Assmann, V:
 Univ Hosp Hamburg Eppendorf, Inst Tumor Biol, Ctr Med Expt, Hamburg, Germany
Stevens, K:
 Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA
Offit, K:
 Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA
Curado, J:
 Biomed Res Pk Barcelona PRBB, Ctr Genom Regulat CRG, Bioinformat & Genom Grp, Barcelona, Catalonia, Spain
Tilgner, H:
 Biomed Res Pk Barcelona PRBB, Ctr Genom Regulat CRG, Bioinformat & Genom Grp, Barcelona, Catalonia, Spain
Guigo, R:
 Biomed Res Pk Barcelona PRBB, Ctr Genom Regulat CRG, Bioinformat & Genom Grp, Barcelona, Catalonia, Spain
Aiza, G:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Brunet, J:
 Girona Biomed Res Inst IdIBGi, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Genet Counseling & Hereditary Canc Programme, Catalonia, Spain
Castellsague, J:
 Girona Biomed Res Inst IdIBGi, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Genet Counseling & Hereditary Canc Programme, Catalonia, Spain
Martrat, G:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Urruticoechea, A:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain
Blanco, I:
 Girona Biomed Res Inst IdIBGi, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Genet Counseling & Hereditary Canc Programme, Catalonia, Spain
Tihomirova, L:
 Latvian Biomed Res & Study Ctr, Riga, Latvia
Goldgar, DE:
 Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA
Buys, S:
 Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT USA
John, EM:
 Canc Prevent Inst Calif, Fremont, CA USA
Miron, A:
 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA
Southey, M:
 Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt MEGA Epidemiol, Melbourne, Vic 3010, Australia
Daly, MB:
 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA
Schmutzler, RK:
 Univ Cologne, Ctr Familial Breast & Ovarian Canc, D-50931 Cologne, Germany

 Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany
Wappenschmidt, B:
 Univ Cologne, Ctr Familial Breast & Ovarian Canc, D-50931 Cologne, Germany

 Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany
Meindl, A:
 Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, D-8000 Munich, Germany
Arnold, N:
 Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Div Oncol, Kiel, Germany
Deissler, H:
 Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany
Varon-Mateeva, R:
 Charite, Inst Humangenet, D-13353 Berlin, Germany
Sutter, C:
 Heidelberg Univ, Inst Human Genet, Heidelberg, Germany
Niederacher, D:
 Univ Dusseldorf, Ctr Clin, Dept Obstet & Gynaecol, Div Mol Genet, D-40225 Dusseldorf, Germany
Imyamitov, E:
 NN Petrov Inst Oncol, St Petersburg, Russia
Sinilnikova, OM:
 CHU Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France

 Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Labellisee LIGUE 2008, Lyon, France
Stoppa-Lyonne, D:
 Univ Paris 05, Serv Genet Oncol, INSERM, Inst Curie,U509, Paris, France
Mazoyer, S:
 Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Labellisee LIGUE 2008, Lyon, France
Verny-Pierre, C:
 Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Labellisee LIGUE 2008, Lyon, France
Castera, L:
 Univ Paris 05, Serv Genet Oncol, INSERM, Inst Curie,U509, Paris, France
de Pauw, A:
 Univ Paris 05, Serv Genet Oncol, INSERM, Inst Curie,U509, Paris, France
Bignon, YJ:
 Univ Clermont Ferrand 2, Ctr Jean Perrin, Dept Oncogenet, Clermont Ferrand, France
Uhrhammer, N:
 Univ Clermont Ferrand 2, Ctr Jean Perrin, Dept Oncogenet, Clermont Ferrand, France
Peyrat, JP:
 Ctr Oscar Lambret, Lab Oncol Mol Humaine, F-59020 Lille, France
Ferrer, SF:
 Hotel Dieu Ctr Hosp, Lab Genet Chromosom, Chambery, France
Collonge-Rame, MA:
 CHU Besancon, Serv Genet Histol Biol Dev & Reprod, F-25030 Besancon, France
Mortemousque, I:
 CHU Bretonneau, Serv Genet, F-37044 Tours, France
Spurdle, AB:
 Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Beesley, J:
 Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Chen, XQ:
 Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Healey, S:
 Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Barcellos-Hoff, MH:
 Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
Vidal, M:
 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

 Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

 Harvard Univ, Sch Med, Ctr Canc Syst Biol CCSB, Boston, MA USA
Gruber, SB:
 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
Lazaro, C:
 Girona Biomed Res Inst IdIBGi, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Genet Counseling & Hereditary Canc Programme, Catalonia, Spain
Capella, G:
 Girona Biomed Res Inst IdIBGi, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Genet Counseling & Hereditary Canc Programme, Catalonia, Spain
McGuffog, L:
 Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Nathanson, KL:
 Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Antoniou, AC:
 Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
Chenevix-Trench, G:
 Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Fleisch, MC:
 Univ Dusseldorf, Dept Obstet & Gynaecol, D-40225 Dusseldorf, Germany
Moreno, V:
 IDIBELL, Catalan Inst Oncol, Biomarkers & Susceptibil Unit, Lhospitalet De Llobregat, Catalonia, Spain
Pujana, MA:
 Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain

 IDIBELL, Catalan Inst Oncol, Biomarkers & Susceptibil Unit, Lhospitalet De Llobregat, Catalonia, Spain
Peter MacCallum Canc Inst, Kathleen Cuningham Fdn, Consortium Res Familial Breast Canc, Melbourne, Australia.
ISSN: 15457885





PLOS BIOLOGY
Editorial
PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA, Estados Unidos America
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Volumen: 9 Número: 11
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WOS Id: 000298152600012
ID de PubMed: 22110403
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