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Interplay between B...
Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
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Maxwell, Christopher A. (author)
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Benitez, Javier (author)
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Gomez-Baldo, Laia (author)
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show more...
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Osorio, Ana (author)
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Bonifaci, Nuria (author)
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Fernandez-Ramires, Ricardo (author)
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Costes, Sylvain V. (author)
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Guino, Elisabet (author)
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Chen, Helen (author)
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Evans, Gareth J. R. (author)
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Mohan, Pooja (author)
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Catala, Isabel (author)
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Petit, Anna (author)
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Aguilar, Helena (author)
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Villanueva, Alberto (author)
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Aytes, Alvaro (author)
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Serra-Musach, Jordi (author)
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Rennert, Gad (author)
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Lejbkowicz, Flavio (author)
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Peterlongo, Paolo (author)
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Manoukian, Siranoush (author)
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Peissel, Bernard (author)
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Ripamonti, Carla B. (author)
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Bonanni, Bernardo (author)
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Viel, Alessandra (author)
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Allavena, Anna (author)
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Bernard, Loris (author)
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Radice, Paolo (author)
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Friedman, Eitan (author)
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Kaufman, Bella (author)
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Laitman, Yael (author)
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Dubrovsky, Maya (author)
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Milgrom, Roni (author)
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Jakubowska, Anna (author)
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Cybulski, Cezary (author)
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Gorski, Bohdan (author)
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Jaworska, Katarzyna (author)
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Durda, Katarzyna (author)
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Sukiennicki, Grzegorz (author)
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Lubinski, Jan (author)
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Shugart, Yin Yao (author)
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Domchek, Susan M. (author)
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Letrero, Richard (author)
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Weber, Barbara L. (author)
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Hogervorst, Frans B. L. (author)
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Rookus, Matti A. (author)
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Collee, J. Margriet (author)
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Devilee, Peter (author)
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Ligtenberg, Marjolijn J. (author)
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van der Luijt, Rob B. (author)
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Aalfs, Cora M. (author)
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Waisfisz, Quinten (author)
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Wijnen, Juul (author)
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van Roozendaal, Cornelis E. P. (author)
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Easton, Douglas F. (author)
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Peock, Susan (author)
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Cook, Margaret (author)
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Oliver, Clare (author)
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Frost, Debra (author)
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Harrington, Patricia (author)
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Evans, D. Gareth (author)
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Lalloo, Fiona (author)
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Eeles, Rosalind (author)
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Izatt, Louise (author)
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Chu, Carol (author)
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Eccles, Diana (author)
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Douglas, Fiona (author)
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Brewer, Carole (author)
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Nevanlinna, Heli (author)
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Heikkinen, Tuomas (author)
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Couch, Fergus J. (author)
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Lindor, Noralane M. (author)
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Wang, Xianshu (author)
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Godwin, Andrew K. (author)
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Caligo, Maria A. (author)
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Lombardi, Grazia (author)
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- Loman, Niklas (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
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- Karlsson, Per, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Ehrencrona, Hans (author)
- Uppsala universitet,Uppsala University,Medicinsk genetik
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von Wachenfeldt, Anna (author)
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Barkardottir, Rosa Bjork (author)
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Hamann, Ute (author)
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Rashid, Muhammad U. (author)
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Lasa, Adriana (author)
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Caldes, Trinidad (author)
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Andres, Raquel (author)
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Schmitt, Michael (author)
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Assmann, Volker (author)
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Stevens, Kristen (author)
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Offit, Kenneth (author)
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Curado, Joao (author)
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Tilgner, Hagen (author)
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Guigo, Roderic (author)
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Aiza, Gemma (author)
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Brunet, Joan (author)
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Castellsague, Joan (author)
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Martrat, Griselda (author)
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Urruticoechea, Ander (author)
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Blanco, Ignacio (author)
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Tihomirova, Laima (author)
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Goldgar, David E. (author)
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Buys, Saundra (author)
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John, Esther M. (author)
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Miron, Alexander (author)
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Southey, Melissa (author)
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Daly, Mary B. (author)
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Schmutzler, Rita K. (author)
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Wappenschmidt, Barbara (author)
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Meindl, Alfons (author)
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Arnold, Norbert (author)
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Deissler, Helmut (author)
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Varon-Mateeva, Raymonda (author)
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Sutter, Christian (author)
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Niederacher, Dieter (author)
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Imyamitov, Evgeny (author)
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Sinilnikova, Olga M. (author)
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Stoppa-Lyonne, Dominique (author)
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Mazoyer, Sylvie (author)
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Verny-Pierre, Carole (author)
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Castera, Laurent (author)
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de Pauw, Antoine (author)
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Bignon, Yves-Jean (author)
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Uhrhammer, Nancy (author)
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Peyrat, Jean-Philippe (author)
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Vennin, Philippe (author)
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Ferrer, Sandra Fert (author)
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Collonge-Rame, Marie-Agnes (author)
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Mortemousque, Isabelle (author)
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Spurdle, Amanda B. (author)
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Beesley, Jonathan (author)
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Chen, Xiaoqing (author)
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Healey, Sue (author)
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Barcellos-Hoff, Mary Helen (author)
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Vidal, Marc (author)
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Gruber, Stephen B. (author)
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Lazaro, Conxi (author)
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Capella, Gabriel (author)
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McGuffog, Lesley (author)
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Nathanson, Katherine L. (author)
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Antoniou, Antonis C. (author)
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Chenevix-Trench, Georgia (author)
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Fleisch, Markus C. (author)
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Moreno, Victor (author)
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Angel Pujana, Miguel (author)
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(creator_code:org_t)
- 2011-11-15
- 2011
- English.
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In: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
- Related links:
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10... (free)
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https://journals.plo...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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https://urn.kb.se/re...
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Abstract
Subject headings
Close
- 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 ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Genetic Predisposition to Disease
- BRCA2
- BRCA1
- Genes
- Female
- Extracellular Matrix Proteins
- Epithelial Cells
- Cell Polarity
- Tumor
- Cell Line
- Breast Neoplasms
- Breast
- BRCA2 Protein
- CD44
- Antigens
- BRCA1 Protein
- Genetic Variation
- Genotype
- HeLa Cells
- Heterozygote
- Humans
- Microtubules
- Protein-Serine-Threonine Kinases
- Receptors
- Estrogen
Publication and Content Type
- art (subject category)
- ref (subject category)
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Maxwell, Christo ...
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Benitez, Javier
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Gomez-Baldo, Lai ...
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Osorio, Ana
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Laitman, Yael
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Dubrovsky, Maya
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Milgrom, Roni
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Rookus, Matti A.
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van der Luijt, R ...
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Aalfs, Cora M.
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Wijnen, Juul
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van Roozendaal, ...
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Peock, Susan
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Oliver, Clare
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Frost, Debra
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Evans, D. Gareth
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Lalloo, Fiona
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Eeles, Rosalind
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Izatt, Louise
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Chu, Carol
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Eccles, Diana
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Douglas, Fiona
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Brewer, Carole
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Nevanlinna, Heli
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Heikkinen, Tuoma ...
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Couch, Fergus J.
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Lindor, Noralane ...
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Wang, Xianshu
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Godwin, Andrew K ...
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Caligo, Maria A.
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Lombardi, Grazia
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Loman, Niklas
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Karlsson, Per, 1 ...
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Ehrencrona, Hans
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von Wachenfeldt, ...
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Barkardottir, Ro ...
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Hamann, Ute
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Rashid, Muhammad ...
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Lasa, Adriana
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Caldes, Trinidad
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Andres, Raquel
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Schmitt, Michael
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Assmann, Volker
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Stevens, Kristen
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Offit, Kenneth
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Curado, Joao
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Tilgner, Hagen
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Guigo, Roderic
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Aiza, Gemma
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Brunet, Joan
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Castellsague, Jo ...
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Martrat, Griseld ...
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Urruticoechea, A ...
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Blanco, Ignacio
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Tihomirova, Laim ...
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Goldgar, David E ...
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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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Schmutzler, Rita ...
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Wappenschmidt, B ...
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Meindl, Alfons
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Arnold, Norbert
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Deissler, Helmut
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Varon-Mateeva, R ...
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Sutter, Christia ...
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Imyamitov, Evgen ...
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Sinilnikova, Olg ...
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Stoppa-Lyonne, D ...
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Mazoyer, Sylvie
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Verny-Pierre, Ca ...
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Ferrer, Sandra F ...
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- NATURAL SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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PLoS Biology
- By the university
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Lund University
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University of Gothenburg
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Uppsala University