13 results on '"Heyn, H."'
Search Results
2. Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells
- Author
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Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X., Palomo-Ponce, S., Mulholland, E.J., Turon, G., Mateo, L., Conti, S., Roman, O., Sevillano, M., Slebe, F., Stork, d., Caballé-Mestres, A., Berenguer-Llergo, A., Álvarez-Varela, A., Fenderico, A., Novellasdemunt, l., Jiménez-Gracia, L., Sipka, T., Bardia, L., Lorden, P., Colombelli, J., Heyn, H., Trepat, X., Tejpar, S., Sancho, E., Tauriello, D.V.F., Leedham, S., Stephan-Otto Attolini, C., Batlle, E., Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X., Palomo-Ponce, S., Mulholland, E.J., Turon, G., Mateo, L., Conti, S., Roman, O., Sevillano, M., Slebe, F., Stork, d., Caballé-Mestres, A., Berenguer-Llergo, A., Álvarez-Varela, A., Fenderico, A., Novellasdemunt, l., Jiménez-Gracia, L., Sipka, T., Bardia, L., Lorden, P., Colombelli, J., Heyn, H., Trepat, X., Tejpar, S., Sancho, E., Tauriello, D.V.F., Leedham, S., Stephan-Otto Attolini, C., and Batlle, E.
- Abstract
Item does not contain fulltext
- Published
- 2022
3. Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells
- Author
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Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X., Palomo-Ponce, S., Mulholland, E.J., Turon, G., Mateo, L., Conti, S., Roman, O., Sevillano, M., Slebe, F., Stork, d., Caballé-Mestres, A., Berenguer-Llergo, A., Álvarez-Varela, A., Fenderico, A., Novellasdemunt, l., Jiménez-Gracia, L., Sipka, T., Bardia, L., Lorden, P., Colombelli, J., Heyn, H., Trepat, X., Tejpar, S., Sancho, E., Tauriello, D.V.F., Leedham, S., Stephan-Otto Attolini, C., Batlle, E., Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X., Palomo-Ponce, S., Mulholland, E.J., Turon, G., Mateo, L., Conti, S., Roman, O., Sevillano, M., Slebe, F., Stork, d., Caballé-Mestres, A., Berenguer-Llergo, A., Álvarez-Varela, A., Fenderico, A., Novellasdemunt, l., Jiménez-Gracia, L., Sipka, T., Bardia, L., Lorden, P., Colombelli, J., Heyn, H., Trepat, X., Tejpar, S., Sancho, E., Tauriello, D.V.F., Leedham, S., Stephan-Otto Attolini, C., and Batlle, E.
- Abstract
Item does not contain fulltext
- Published
- 2022
4. Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters
- Author
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Robles-Rebollo, I, Cuartero, S, Canellas-Socias, A, Wells, S, Karimi, MM, Mereu, E, Chivu, AG, Heyn, H, Whilding, C, Dormann, D, Marguerat, S, Rioja, I, Prinjha, RK, Stumpf, MPH, Fisher, AG, Merkenschlager, M, Robles-Rebollo, I, Cuartero, S, Canellas-Socias, A, Wells, S, Karimi, MM, Mereu, E, Chivu, AG, Heyn, H, Whilding, C, Dormann, D, Marguerat, S, Rioja, I, Prinjha, RK, Stumpf, MPH, Fisher, AG, and Merkenschlager, M
- Abstract
Innate immune responses rely on inducible gene expression programmes which, in contrast to steady-state transcription, are highly dependent on cohesin. Here we address transcriptional parameters underlying this cohesin-dependence by single-molecule RNA-FISH and single-cell RNA-sequencing. We show that inducible innate immune genes are regulated predominantly by an increase in the probability of active transcription, and that probabilities of enhancer and promoter transcription are coordinated. Cohesin has no major impact on the fraction of transcribed inducible enhancers, or the number of mature mRNAs produced per transcribing cell. Cohesin is, however, required for coupling the probabilities of enhancer and promoter transcription. Enhancer-promoter coupling may not be explained by spatial proximity alone, and at the model locus Il12b can be disrupted by selective inhibition of the cohesinopathy-associated BET bromodomain BD2. Our data identify discrete steps in enhancer-mediated inducible gene expression that differ in cohesin-dependence, and suggest that cohesin and BD2 may act on shared pathways.
- Published
- 2022
5. The emerging landscape of spatial profiling technologies
- Author
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Moffitt, J. R., Lundberg, Emma, Heyn, H., Moffitt, J. R., Lundberg, Emma, and Heyn, H.
- Abstract
Improved scale, multiplexing and resolution are establishing spatial nucleic acid and protein profiling methods as a major pillar for cellular atlas building of complex samples, from tissues to full organisms. Emerging methods yield omics measurements at resolutions covering the nano- to microscale, enabling the charting of cellular heterogeneity, complex tissue architectures and dynamic changes during development and disease. We present an overview of the developing landscape of in situ spatial genome, transcriptome and proteome technologies, exemplify their impact on cell biology and translational research, and discuss current challenges for their community-wide adoption. Among many transformative applications, we envision that spatial methods will map entire organs and enable next-generation pathology., QC 20230421
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- 2022
- Full Text
- View/download PDF
6. Building a high-quality Human Cell Atlas
- Author
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Rozenblatt-Rosen, O., Shin, J. W., Rood, J. E., Hupalowska, A., Ardlie, K., Clatworthy, M., Carninci, P., Enard, W., Greenleaf, W., Heyn, H., Lein, E., Levin, J. Z., Linnarsson, S., Lundberg, Emma, Meyer, K., Navin, N., Nolan, G., Teichmann, S., Voet, T., Zhuang, X., Regev, A., Group, Human Cell Atlas Standards and Technology Working, Rozenblatt-Rosen, O., Shin, J. W., Rood, J. E., Hupalowska, A., Ardlie, K., Clatworthy, M., Carninci, P., Enard, W., Greenleaf, W., Heyn, H., Lein, E., Levin, J. Z., Linnarsson, S., Lundberg, Emma, Meyer, K., Navin, N., Nolan, G., Teichmann, S., Voet, T., Zhuang, X., Regev, A., and Group, Human Cell Atlas Standards and Technology Working
- Abstract
QC 20211116
- Published
- 2021
- Full Text
- View/download PDF
7. LifeTime and improving European healthcare through cell-based interceptive medicine
- Author
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Rajewsky, N., Almouzni, G., Gorski, S. A., Aerts, S., Amit, I., Bertero, M. G., Bock, C., Bredenoord, A. L., Cavalli, G., Chiocca, S., Clevers, H., De Strooper, B., Eggert, A., Ellenberg, J., Fernández, X. M., Figlerowicz, M., Gasser, S. M., Hubner, N., Kjems, J., Knoblich, J. A., Krabbe, G., Lichter, P., Linnarsson, S., Marine, J. -C, Marioni, J., Marti-Renom, M. A., Netea, M. G., Nickel, D., Nollmann, M., Novak, H. R., Parkinson, H., Piccolo, S., Pinheiro, I., Pombo, A., Popp, C., Reik, W., Roman-Roman, S., Rosenstiel, P., Schultze, J. L., Stegle, O., Tanay, A., Testa, G., Thanos, D., Theis, F. J., Torres-Padilla, M. -E, Valencia, A., Vallot, C., van Oudenaarden, A., Vidal, M., Voet, T., Alberi, L., Alexander, S., Alexandrov, T., Arenas, E., Bagni, C., Balderas, R., Bandelli, A., Becher, B., Becker, M., Beerenwinkel, N., Benkirame, M., Beyer, M., Bickmore, W., Biessen, E. E. A. L., Blomberg, N., Blumcke, I., Bodenmiller, B., Borroni, B., Boumpas, D. T., Bourgeron, T., Bowers, S., Braeken, D., Brooksbank, C., Brose, N., Bruining, H., Bury, J., Caporale, N., Cattoretti, G., Chabane, N., Chneiweiss, H., Cook, S. A., Curatolo, P., de Jonge, M. I., Deplancke, B., de Witte, P., Dimmeler, S., Draganski, B., Drews, A. -D, Dumbrava, C., Engelhardt, S., Gasser, T., Giamarellos-Bourboulis, E. J., Graff, C., Grün, D., Gut, I., Hansson, O., Henshall, D. C., Herland, Anna, Heutink, P., Heymans, S. R. B., Heyn, H., Huch, M., Huitinga, I., Jackowiak, P., Jongsma, K. R., Journot, L., Junker, J. P., Katz, S., Kehren, J., Kempa, S., Kirchhof, P., Klein, C., Koralewska, N., Korbel, J. O., Kühnemund, M., Lamond, A. I., Lauwers, E., Le Ber, I., Leinonen, V., Tobon, A. L., Lundberg, E., Lunkes, A., Maatz, H., Mann, M., Marelli, L., Matser, V., Matthews, P. M., Mechta-Grigoriou, F., Menon, R., Nielsen, A. F., Pagani, M., Pasterkamp, R. J., Pitkanen, A., Popescu, V., Pottier, C., Puisieux, A., Rademakers, R., Reiling, D., Reiner, O., Remondini, D., Ritchie, C., Rohrer, J. D., Saliba, A. -E, Sanchez-Valle, R., Santosuosso, A., Sauter, A., Scheltema, R. A., Scheltens, P., Schiller, H. B., Schneider, A., Seibler, P., Sheehan-Rooney, K., Shields, D., Sleegers, K., Smit, G., Smith, K. G. C., Smolders, I., Synofzik, M., Tam, W. L., Teichmann, S., Thom, M., Turco, M. Y., van Beusekom, H. M. M., Vandenberghe, R., den Hoecke, S. V., Van de Poel, I., der Ven, A., van der Zee, J., van Lunzen, J., van Minnebruggen, G., Van Paesschen, W., van Swieten, J., van Vught, R., Verhage, M., Verstreken, P., Villa, C. E., Vogel, J., von Kalle, C., Walter, J., Weckhuysen, S., Weichert, W., Wood, L., Ziegler, A. -G, Zipp, F., Community, LifeTime, Rajewsky, N., Almouzni, G., Gorski, S. A., Aerts, S., Amit, I., Bertero, M. G., Bock, C., Bredenoord, A. L., Cavalli, G., Chiocca, S., Clevers, H., De Strooper, B., Eggert, A., Ellenberg, J., Fernández, X. M., Figlerowicz, M., Gasser, S. M., Hubner, N., Kjems, J., Knoblich, J. A., Krabbe, G., Lichter, P., Linnarsson, S., Marine, J. -C, Marioni, J., Marti-Renom, M. A., Netea, M. G., Nickel, D., Nollmann, M., Novak, H. R., Parkinson, H., Piccolo, S., Pinheiro, I., Pombo, A., Popp, C., Reik, W., Roman-Roman, S., Rosenstiel, P., Schultze, J. L., Stegle, O., Tanay, A., Testa, G., Thanos, D., Theis, F. J., Torres-Padilla, M. -E, Valencia, A., Vallot, C., van Oudenaarden, A., Vidal, M., Voet, T., Alberi, L., Alexander, S., Alexandrov, T., Arenas, E., Bagni, C., Balderas, R., Bandelli, A., Becher, B., Becker, M., Beerenwinkel, N., Benkirame, M., Beyer, M., Bickmore, W., Biessen, E. E. A. L., Blomberg, N., Blumcke, I., Bodenmiller, B., Borroni, B., Boumpas, D. T., Bourgeron, T., Bowers, S., Braeken, D., Brooksbank, C., Brose, N., Bruining, H., Bury, J., Caporale, N., Cattoretti, G., Chabane, N., Chneiweiss, H., Cook, S. A., Curatolo, P., de Jonge, M. I., Deplancke, B., de Witte, P., Dimmeler, S., Draganski, B., Drews, A. -D, Dumbrava, C., Engelhardt, S., Gasser, T., Giamarellos-Bourboulis, E. J., Graff, C., Grün, D., Gut, I., Hansson, O., Henshall, D. C., Herland, Anna, Heutink, P., Heymans, S. R. B., Heyn, H., Huch, M., Huitinga, I., Jackowiak, P., Jongsma, K. R., Journot, L., Junker, J. P., Katz, S., Kehren, J., Kempa, S., Kirchhof, P., Klein, C., Koralewska, N., Korbel, J. O., Kühnemund, M., Lamond, A. I., Lauwers, E., Le Ber, I., Leinonen, V., Tobon, A. L., Lundberg, E., Lunkes, A., Maatz, H., Mann, M., Marelli, L., Matser, V., Matthews, P. M., Mechta-Grigoriou, F., Menon, R., Nielsen, A. F., Pagani, M., Pasterkamp, R. J., Pitkanen, A., Popescu, V., Pottier, C., Puisieux, A., Rademakers, R., Reiling, D., Reiner, O., Remondini, D., Ritchie, C., Rohrer, J. D., Saliba, A. -E, Sanchez-Valle, R., Santosuosso, A., Sauter, A., Scheltema, R. A., Scheltens, P., Schiller, H. B., Schneider, A., Seibler, P., Sheehan-Rooney, K., Shields, D., Sleegers, K., Smit, G., Smith, K. G. C., Smolders, I., Synofzik, M., Tam, W. L., Teichmann, S., Thom, M., Turco, M. Y., van Beusekom, H. M. M., Vandenberghe, R., den Hoecke, S. V., Van de Poel, I., der Ven, A., van der Zee, J., van Lunzen, J., van Minnebruggen, G., Van Paesschen, W., van Swieten, J., van Vught, R., Verhage, M., Verstreken, P., Villa, C. E., Vogel, J., von Kalle, C., Walter, J., Weckhuysen, S., Weichert, W., Wood, L., Ziegler, A. -G, Zipp, F., and Community, LifeTime
- Abstract
LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade., QC 20201117Correction in: Nature, Volume 587, Issue 7834, Pages 377 - 386, 19 November 2020. DOI: 10.1038/s41586-021-03287-8, Scopus ID: 2-s2.0-85102698588
- Published
- 2020
- Full Text
- View/download PDF
8. LifeTime and improving European healthcare through cell-based interceptive medicine
- Author
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Rajewsky, N. (Nikolaus), Almouzni, G. (Geneviève), Gorski, S.A. (Stanislaw A.), Aerts, S. (Stein), Amit, I. (Ido), Bertero, M.G. (Michela G.), Bock, C. (Christoph), Bredenoord, A.L. (Annelien L.), Cavalli, G. (Giacomo), Chiocca, S. (Susanna), Clevers, H.C. (Hans), Strooper, B. (Bart) de, Eggert, A. (Angelika), Ellenberg, J. (Jan), Fernández, X.M. (Xosé M.), Figlerowicz, M. (Marek), Gasser, S.M. (Susan M.), Hübner, N. (Norbert), Kjems, J. (Jørgen), Knoblich, J.A. (Jürgen A.), Krabbe, G. (Grietje), Lichter, P. (Peter), Linnarsson, S. (Sten), Marine, J.-C. (J.), Marioni, J. (John), Marti-Renom, M.A. (Marc A.), Netea, M.G. (Mihai), Nickel, D. (Dörthe), Nollmann, M. (Marcelo), Novak, H.R. (Halina R.), Parkinson, H. (Helen), Piccolo, S. (Stefano), Pinheiro, I. (Inês), Pombo, A. (Ana), Popp, C. (Christian), Reik, W. (Wolf), Roman-Roman, S. (Sergio), Rosenstiel, P. (Philip), Schultze, J.L. (Joachim), Stegle, O. (Oliver), Tanay, A. (Amos), Testa, G. (Giuseppe), Thanos, D. (Dimitris), Theis, F. (Fabian), Torres-Padilla, M.-E. (Maria-Elena), Valencia, A. (Alfonso), Vallot, C. (Céline), van Oudenaarden, A. (Alexander), Vidal, M. (Marie), Voet, T. (Thierry), Alberi, L. (Lavinia), Alexander, S. (Stephanie), Alexandrov, T. (Theodore), Arenas, E. (Ernest), Bagni, C. (Claudia), Balderas, R. (Robert), Bandelli, A. (Andrea), Becher, B. (Burkhard), Becker, M. (Matthias), Beerenwinkel, N. (Niko), Benkirame, M. (Monsef), Beyer, M. (Marc), Bickmore, W. (Wendy), Biessen, E.E.A.L. (Erik E.A.L.), Blomberg, N. (Niklas), Blumcke, I. (Ingmar), Bodenmiller, B. (Bernd), Borroni, B. (Barbara), Boumpas, D.T. (Dimitrios T.), Bourgeron, T. (Thomas), Bowers, S. (Sarion), Braeken, D. (Dries), Brooksbank, C. (Catherine), Brose, N. (Nils), Bruining, J. (Hans), Bury, J. (Jo), Caporale, N. (Nicolo), Cattoretti, G. (Giorgio), Chabane, N. (Nadia), Chneiweiss, H. (Hervé), Cook, S.A. (Stuart A.), Curatolo, P. (Paolo), Jonge, M.I. (Marien) de, Deplancke, B. (Bart), De Strooper, B. (Bart), de Witte, P. (Peter), Dimmeler, S. (Stefanie), Draganski, B. (Bogdan), Drews, A.-D. (Anna-Dorothee), Dumbrava, C. (Costica), Engelhardt, S. (Stefan), Gasser, T. (Thomas), Giamarellos-Bourboulis, E. (Evangelos), Graff, C. (Caroline), Grün, D. (Dominic), Gut, I. (Ivo), Hansson, O. (Oskar), Henshall, D.C. (David C.), Herland, A. (Anna), Heutink, P. (Peter), Heymans, S. (Stephane), Heyn, H. (Holger), Huch, M. (Meritxell), Huitinga, I. (Inge), Jackowiak, P. (Paulina), Jongsma, K.R. (Karin), Journot, L. (Laurent), Junker, J.P. (Jan Philipp), Katz, S. (Shauna), Kehren, J. (Jeanne), Kempa, S. (Stefan), Kirchhof, P. (Paulus), Klein, C. (Christoph), Koralewska, N. (Natalia), Korbel, J.O. (Jan), Kühnemund, M. (Malte), Lamond, A.I. (Angus I.), Lauwers, E. (Elsa), Le Ber, I. (Isabelle), Leinonen, V. (Ville), Tobon, A.L. (Alejandro Lopez), Lundberg, E. (Emma), Lunkes, A. (Astrid), Maatz, H. (Henrike), Mann, M. (Mathias), Marelli, L. (Luca), Matser, V. (Vera), Matthews, P.M. (P.), Mechta-Grigoriou, F. (Fatima), Menon, R. (Radhika), Nielsen, A.F. (Anne F.), Pagani, M. (Massimiliano), Pasterkamp, R.J. (Jeroen), Pitkanen, A. (Asla), Popescu, V. (Valentin), Pottier, C. (Cyril), Puisieux, A. (Alain), Rademakers, R. (Rosa), Reiling, D. (Dory), Reiner, O. (Orly), Remondini, D. (Daniel), Ritchie, C. (Craig), Rohrer, J.D. (Jonathan D.), Saliba, A.-E. (Antione-Emmanuel), Sánchez-Valle, R. (Raquel), Santosuosso, A. (Amedeo), Sauter, A. (Arnold), Scheltema, R.A. (Richard A.), Scheltens, P. (Philip), Schiller, H.B. (Herbert B.), Schneider, A. (Anja), Seibler, P. (Philip), Sheehan-Rooney, K. (Kelly), Shields, D. (David), Sleegers, K. (Kristel), Smit, G. (Guus), Smith, K.G.C. (Kenneth G. C.), Smolders, I. (Ilse), Synofzik, M. (Matthis), Tam, W.L. (Wai Long), Teichmann, S. (Sarah), Thom, M. (Maria), Turco, M.Y. (Margherita Y.), Beusekom, H.M.M. (Heleen) van, Vandenberghe, R. (Rik), den Hoecke, S.V. (Silvie Van), Van de Poel, E. (Ellen), der Ven, A. (Andre van), van der Zee, J. (Julie), van Lunzen, J. (Jan), van Minnebruggen, G. (Geert), Van Paesschen, W. (Wim), Swieten, J.C. (John) van, van Vught, R. (Remko), Verhage, M. (Matthijs), Verstreken, P. (Patrik), Villa, C.E. (Carlo Emanuele), Vogel, J. (Jörg), Kalle, C. (Christof) von, Walter, J. (Jörn), Weckhuysen, S. (Sarah), Weichert, W. (Wilko), Wood, L. (Louisa), Ziegler, A.-G. (Anette-Gabriele), Zipp, F. (Frauke), Rajewsky, N. (Nikolaus), Almouzni, G. (Geneviève), Gorski, S.A. (Stanislaw A.), Aerts, S. (Stein), Amit, I. (Ido), Bertero, M.G. (Michela G.), Bock, C. (Christoph), Bredenoord, A.L. (Annelien L.), Cavalli, G. (Giacomo), Chiocca, S. (Susanna), Clevers, H.C. (Hans), Strooper, B. (Bart) de, Eggert, A. (Angelika), Ellenberg, J. (Jan), Fernández, X.M. (Xosé M.), Figlerowicz, M. (Marek), Gasser, S.M. (Susan M.), Hübner, N. (Norbert), Kjems, J. (Jørgen), Knoblich, J.A. (Jürgen A.), Krabbe, G. (Grietje), Lichter, P. (Peter), Linnarsson, S. (Sten), Marine, J.-C. (J.), Marioni, J. (John), Marti-Renom, M.A. (Marc A.), Netea, M.G. (Mihai), Nickel, D. (Dörthe), Nollmann, M. (Marcelo), Novak, H.R. (Halina R.), Parkinson, H. (Helen), Piccolo, S. (Stefano), Pinheiro, I. (Inês), Pombo, A. (Ana), Popp, C. (Christian), Reik, W. (Wolf), Roman-Roman, S. (Sergio), Rosenstiel, P. (Philip), Schultze, J.L. (Joachim), Stegle, O. (Oliver), Tanay, A. (Amos), Testa, G. (Giuseppe), Thanos, D. (Dimitris), Theis, F. (Fabian), Torres-Padilla, M.-E. (Maria-Elena), Valencia, A. (Alfonso), Vallot, C. (Céline), van Oudenaarden, A. (Alexander), Vidal, M. (Marie), Voet, T. (Thierry), Alberi, L. (Lavinia), Alexander, S. (Stephanie), Alexandrov, T. (Theodore), Arenas, E. (Ernest), Bagni, C. (Claudia), Balderas, R. (Robert), Bandelli, A. (Andrea), Becher, B. (Burkhard), Becker, M. (Matthias), Beerenwinkel, N. (Niko), Benkirame, M. (Monsef), Beyer, M. (Marc), Bickmore, W. (Wendy), Biessen, E.E.A.L. (Erik E.A.L.), Blomberg, N. (Niklas), Blumcke, I. (Ingmar), Bodenmiller, B. (Bernd), Borroni, B. (Barbara), Boumpas, D.T. (Dimitrios T.), Bourgeron, T. (Thomas), Bowers, S. (Sarion), Braeken, D. (Dries), Brooksbank, C. (Catherine), Brose, N. (Nils), Bruining, J. (Hans), Bury, J. (Jo), Caporale, N. (Nicolo), Cattoretti, G. (Giorgio), Chabane, N. (Nadia), Chneiweiss, H. (Hervé), Cook, S.A. (Stuart A.), Curatolo, P. (Paolo), Jonge, M.I. (Marien) de, Deplancke, B. (Bart), De Strooper, B. (Bart), de Witte, P. (Peter), Dimmeler, S. (Stefanie), Draganski, B. (Bogdan), Drews, A.-D. (Anna-Dorothee), Dumbrava, C. (Costica), Engelhardt, S. (Stefan), Gasser, T. (Thomas), Giamarellos-Bourboulis, E. (Evangelos), Graff, C. (Caroline), Grün, D. (Dominic), Gut, I. (Ivo), Hansson, O. (Oskar), Henshall, D.C. (David C.), Herland, A. (Anna), Heutink, P. (Peter), Heymans, S. (Stephane), Heyn, H. (Holger), Huch, M. (Meritxell), Huitinga, I. (Inge), Jackowiak, P. (Paulina), Jongsma, K.R. (Karin), Journot, L. (Laurent), Junker, J.P. (Jan Philipp), Katz, S. (Shauna), Kehren, J. (Jeanne), Kempa, S. (Stefan), Kirchhof, P. (Paulus), Klein, C. (Christoph), Koralewska, N. (Natalia), Korbel, J.O. (Jan), Kühnemund, M. (Malte), Lamond, A.I. (Angus I.), Lauwers, E. (Elsa), Le Ber, I. (Isabelle), Leinonen, V. (Ville), Tobon, A.L. (Alejandro Lopez), Lundberg, E. (Emma), Lunkes, A. (Astrid), Maatz, H. (Henrike), Mann, M. (Mathias), Marelli, L. (Luca), Matser, V. (Vera), Matthews, P.M. (P.), Mechta-Grigoriou, F. (Fatima), Menon, R. (Radhika), Nielsen, A.F. (Anne F.), Pagani, M. (Massimiliano), Pasterkamp, R.J. (Jeroen), Pitkanen, A. (Asla), Popescu, V. (Valentin), Pottier, C. (Cyril), Puisieux, A. (Alain), Rademakers, R. (Rosa), Reiling, D. (Dory), Reiner, O. (Orly), Remondini, D. (Daniel), Ritchie, C. (Craig), Rohrer, J.D. (Jonathan D.), Saliba, A.-E. (Antione-Emmanuel), Sánchez-Valle, R. (Raquel), Santosuosso, A. (Amedeo), Sauter, A. (Arnold), Scheltema, R.A. (Richard A.), Scheltens, P. (Philip), Schiller, H.B. (Herbert B.), Schneider, A. (Anja), Seibler, P. (Philip), Sheehan-Rooney, K. (Kelly), Shields, D. (David), Sleegers, K. (Kristel), Smit, G. (Guus), Smith, K.G.C. (Kenneth G. C.), Smolders, I. (Ilse), Synofzik, M. (Matthis), Tam, W.L. (Wai Long), Teichmann, S. (Sarah), Thom, M. (Maria), Turco, M.Y. (Margherita Y.), Beusekom, H.M.M. (Heleen) van, Vandenberghe, R. (Rik), den Hoecke, S.V. (Silvie Van), Van de Poel, E. (Ellen), der Ven, A. (Andre van), van der Zee, J. (Julie), van Lunzen, J. (Jan), van Minnebruggen, G. (Geert), Van Paesschen, W. (Wim), Swieten, J.C. (John) van, van Vught, R. (Remko), Verhage, M. (Matthijs), Verstreken, P. (Patrik), Villa, C.E. (Carlo Emanuele), Vogel, J. (Jörg), Kalle, C. (Christof) von, Walter, J. (Jörn), Weckhuysen, S. (Sarah), Weichert, W. (Wilko), Wood, L. (Louisa), Ziegler, A.-G. (Anette-Gabriele), and Zipp, F. (Frauke)
- Abstract
LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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- 2020
- Full Text
- View/download PDF
9. Benchmarking single-cell RNA-sequencing protocols for cell atlas projects
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Mereu, E, Lafzi, A, Moutinho, C, Ziegenhain, C, McCarthy, DJ, Alvarez-Varela, A, Batlle, E, Sagar, Gruen, D, Lau, JK, Boutet, SC, Sanada, C, Ooi, A, Jones, RC, Kaihara, K, Brampton, C, Talaga, Y, Sasagawa, Y, Tanaka, K, Hayashi, T, Braeuning, C, Fischer, C, Sauers, S, Trefzer, T, Conrad, C, Adiconis, X, Nguyen, LT, Regev, A, Levin, JZ, Parekh, S, Janjic, A, Wange, LE, Bagnoli, JW, Enard, W, Gut, M, Sandberg, R, Nikaido, I, Gut, I, Stegle, O, Heyn, H, Mereu, E, Lafzi, A, Moutinho, C, Ziegenhain, C, McCarthy, DJ, Alvarez-Varela, A, Batlle, E, Sagar, Gruen, D, Lau, JK, Boutet, SC, Sanada, C, Ooi, A, Jones, RC, Kaihara, K, Brampton, C, Talaga, Y, Sasagawa, Y, Tanaka, K, Hayashi, T, Braeuning, C, Fischer, C, Sauers, S, Trefzer, T, Conrad, C, Adiconis, X, Nguyen, LT, Regev, A, Levin, JZ, Parekh, S, Janjic, A, Wange, LE, Bagnoli, JW, Enard, W, Gut, M, Sandberg, R, Nikaido, I, Gut, I, Stegle, O, and Heyn, H
- Abstract
Single-cell RNA sequencing (scRNA-seq) is the leading technique for characterizing the transcriptomes of individual cells in a sample. The latest protocols are scalable to thousands of cells and are being used to compile cell atlases of tissues, organs and organisms. However, the protocols differ substantially with respect to their RNA capture efficiency, bias, scale and costs, and their relative advantages for different applications are unclear. In the present study, we generated benchmark datasets to systematically evaluate protocols in terms of their power to comprehensively describe cell types and states. We performed a multicenter study comparing 13 commonly used scRNA-seq and single-nucleus RNA-seq protocols applied to a heterogeneous reference sample resource. Comparative analysis revealed marked differences in protocol performance. The protocols differed in library complexity and their ability to detect cell-type markers, impacting their predictive value and suitability for integration into reference cell atlases. These results provide guidance both for individual researchers and for consortium projects such as the Human Cell Atlas.
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- 2020
10. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns
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Sanchez-Mut, J V, Sanchez-Mut, J V, Heyn, H, Vidal, E, Moran, S, Sayols, S, Delgado-Morales, R, Schultz, M D, Ansoleaga, B, Garcia-Esparcia, P, Pons-Espinal, M, de Lagran, M M, Dopazo, J, Rabano, A, Avila, J, Dierssen, M, Lott, I, Ferrer, I, Ecker, J R, Esteller, M, Sanchez-Mut, J V, Sanchez-Mut, J V, Heyn, H, Vidal, E, Moran, S, Sayols, S, Delgado-Morales, R, Schultz, M D, Ansoleaga, B, Garcia-Esparcia, P, Pons-Espinal, M, de Lagran, M M, Dopazo, J, Rabano, A, Avila, J, Dierssen, M, Lott, I, Ferrer, I, Ecker, J R, and Esteller, M
- Published
- 2016
11. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns
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Sanchez-Mut, J V, Sanchez-Mut, J V, Heyn, H, Vidal, E, Moran, S, Sayols, S, Delgado-Morales, R, Schultz, M D, Ansoleaga, B, Garcia-Esparcia, P, Pons-Espinal, M, de Lagran, M M, Dopazo, J, Rabano, A, Avila, J, Dierssen, M, Lott, I, Ferrer, I, Ecker, J R, Esteller, M, Sanchez-Mut, J V, Sanchez-Mut, J V, Heyn, H, Vidal, E, Moran, S, Sayols, S, Delgado-Morales, R, Schultz, M D, Ansoleaga, B, Garcia-Esparcia, P, Pons-Espinal, M, de Lagran, M M, Dopazo, J, Rabano, A, Avila, J, Dierssen, M, Lott, I, Ferrer, I, Ecker, J R, and Esteller, M
- Published
- 2016
12. Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
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Blanco, I. (Ignacio), Kuchenbaecker, K.B. (Karoline), Cuadras, D. (Daniel), Wang, X. (Xing), Barrowdale, D. (Daniel), De Garibay, G.R. (Gorka Ruiz), Librado, P. (Pablo), Sánchez-Gracia, A. (Alejandro), Rozas, J. (Julio), Bonifaci, N. (Núria), McGuffog, L. (Lesley), Pankratz, V.S. (Shane), Islam, A.B.M.M.K. (Abul), Mateo, F. (Francesca), Berenguer, A. (Antonio), Petit, A. (Anna), Català, I. (Isabel), Brunet, J. (Joan), Feliubadaló, L. (L.), Tornero, E. (Eva), Benítez, J. (Javier), Osorio, A. (Ana), Teresa, R. (Ramón), Teresa, C. (Cajal), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Arun, B.K. (Banu), Toland, A.E. (Amanda), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Greene, M.H. (Mark), Mai, P.L. (Phuong), Nussbaum, R.L. (Robert L.), Andrulis, I.L. (Irene), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Barkardottir, R.B. (Rosa), Jakubowska, A. (Anna), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Claes, K. (Kathleen), Van Maerken, T. (Tom), Díez, O. (Orland), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Dunning, A.M. (Alison), Oliver, C.T. (Clare), Fineberg, E. (Elena), Cook, M. (Margaret), Peock, S. (Susan), McCann, E. (Emma), Murray, A. (Alexandra), Jacobs, C. (Chris), Pichert, G. (Gabriella), Lalloo, F. (Fiona), Chu, C. (Carol), Dorkins, H. (Huw), Paterson, J. (Joan), Ong, K.-R. (Kai-Ren), Teixeira, M.R. (Manuel R.), Teixeira, T. (T.), Hogervorst, F.B.L. (Frans), Hout, A.H. (Annemarie) van der, Seynaeve, C.M. (Caroline), Van Der Luijt, R.B. (Rob B.), Ligtenberg, M.J. (Marjolijn), Devilee, P. (Peter), Wijnen, J.T. (Juul), Rookus, M.A. (Matti), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Ouweland, A.M.W. (Ans) van den, Aalfs, C.M. (Cora), Rodriguez, G.C. (Gustavo C.), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Nerenstone, S. (Stacy), Bae-Jump, V.L. (Victoria L.), O'Malley, D.M. (David M.), Ratner, E.S. (Elena S.), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Jensen, U.B., Thomassen, M. (Mads), Kruse, T.A. (Torben), Foretova, L. (Lenka), Peterlongo, P. (Paolo), Bernard, L. (Loris), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Radice, P. (Paolo), Ottini, L. (Laura), Montagna, M. (Marco), Agata, S. (Simona), Maugard, C., Simard, J. (Jacques), Soucy, P. (Penny), Berger, A. (Annemarie), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Tea, M.-K., Pfeiler, G. (Georg), John, E.M. (Esther), Miron, A. (Alexander), Neuhausen, S.L. (Susan), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Daly, M.B. (Mary), Goldgar, D. (David), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J., Godwin, A.K. (Andrew), Olah, E., Narod, S.A. (Steven A.), Rennert, G. (Gad), Paluch, S.S. (Shani), Laitman, Y. (Yael), Friedman, E. (Eitan), Liljegren, A. (Annelie), Rantala, J. (Johanna), Stenmark-Askmalm, M. (Marie), Loman, N. (Niklas), Imyanitov, E.N. (Evgeny), Hamann, U. (Ute), Spurdle, A.B. (Amanda), Healey, S. (Sue), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Margileth, D. (David), Gorrini, C. (Chiara), Esteller, M. (Manel), Gómez, A. (Antonio), Sayols, S. (Sergi), Vidal, E. (Enrique), Heyn, H. (Holger), Stoppa-Lyonnet, D. (Dominique), Léone, M. (Mélanie), Barjhoux, L. (Laure), Fassy-Colcombet, M. (Marion), Pauw, A. (Antoine) de, Lasset, C. (Christine), Ferrer, S.F., Castera, L. (Laurent), Berthet, P. (Pascaline), Cornelis, F. (Franco̧is), Bignon, Y.-J. (Yves-Jean), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Maxwell, C.A. (Christopher), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Corines, M.J. (Marina J.), Villano, D. (Danylko), Cunningham, J.M. (Julie), Lee, A. (Adam), Lindor, N.M. (Noralane), Lázaro, C. (Conxi), Easton, D.F. (Douglas), Offit, K. (Kenneth), Chenevix-Trench, G. (Georgia), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis C.), Pujana, M.A. (Miguel), Blanco, I. (Ignacio), Kuchenbaecker, K.B. (Karoline), Cuadras, D. (Daniel), Wang, X. (Xing), Barrowdale, D. (Daniel), De Garibay, G.R. (Gorka Ruiz), Librado, P. (Pablo), Sánchez-Gracia, A. (Alejandro), Rozas, J. (Julio), Bonifaci, N. (Núria), McGuffog, L. (Lesley), Pankratz, V.S. (Shane), Islam, A.B.M.M.K. (Abul), Mateo, F. (Francesca), Berenguer, A. (Antonio), Petit, A. (Anna), Català, I. (Isabel), Brunet, J. (Joan), Feliubadaló, L. (L.), Tornero, E. (Eva), Benítez, J. (Javier), Osorio, A. (Ana), Teresa, R. (Ramón), Teresa, C. (Cajal), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Arun, B.K. (Banu), Toland, A.E. (Amanda), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Greene, M.H. (Mark), Mai, P.L. (Phuong), Nussbaum, R.L. (Robert L.), Andrulis, I.L. (Irene), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Barkardottir, R.B. (Rosa), Jakubowska, A. (Anna), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Claes, K. (Kathleen), Van Maerken, T. (Tom), Díez, O. (Orland), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Dunning, A.M. (Alison), Oliver, C.T. (Clare), Fineberg, E. (Elena), Cook, M. (Margaret), Peock, S. (Susan), McCann, E. (Emma), Murray, A. (Alexandra), Jacobs, C. (Chris), Pichert, G. (Gabriella), Lalloo, F. (Fiona), Chu, C. (Carol), Dorkins, H. (Huw), Paterson, J. (Joan), Ong, K.-R. (Kai-Ren), Teixeira, M.R. (Manuel R.), Teixeira, T. (T.), Hogervorst, F.B.L. (Frans), Hout, A.H. (Annemarie) van der, Seynaeve, C.M. (Caroline), Van Der Luijt, R.B. (Rob B.), Ligtenberg, M.J. (Marjolijn), Devilee, P. (Peter), Wijnen, J.T. (Juul), Rookus, M.A. (Matti), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Ouweland, A.M.W. (Ans) van den, Aalfs, C.M. (Cora), Rodriguez, G.C. (Gustavo C.), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Nerenstone, S. (Stacy), Bae-Jump, V.L. (Victoria L.), O'Malley, D.M. (David M.), Ratner, E.S. (Elena S.), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Jensen, U.B., Thomassen, M. (Mads), Kruse, T.A. (Torben), Foretova, L. (Lenka), Peterlongo, P. (Paolo), Bernard, L. (Loris), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Radice, P. (Paolo), Ottini, L. (Laura), Montagna, M. (Marco), Agata, S. (Simona), Maugard, C., Simard, J. (Jacques), Soucy, P. (Penny), Berger, A. (Annemarie), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Tea, M.-K., Pfeiler, G. (Georg), John, E.M. (Esther), Miron, A. (Alexander), Neuhausen, S.L. (Susan), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Daly, M.B. (Mary), Goldgar, D. (David), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J., Godwin, A.K. (Andrew), Olah, E., Narod, S.A. (Steven A.), Rennert, G. (Gad), Paluch, S.S. (Shani), Laitman, Y. (Yael), Friedman, E. (Eitan), Liljegren, A. (Annelie), Rantala, J. (Johanna), Stenmark-Askmalm, M. (Marie), Loman, N. (Niklas), Imyanitov, E.N. (Evgeny), Hamann, U. (Ute), Spurdle, A.B. (Amanda), Healey, S. (Sue), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Margileth, D. (David), Gorrini, C. (Chiara), Esteller, M. (Manel), Gómez, A. (Antonio), Sayols, S. (Sergi), Vidal, E. (Enrique), Heyn, H. (Holger), Stoppa-Lyonnet, D. (Dominique), Léone, M. (Mélanie), Barjhoux, L. (Laure), Fassy-Colcombet, M. (Marion), Pauw, A. (Antoine) de, Lasset, C. (Christine), Ferrer, S.F., Castera, L. (Laurent), Berthet, P. (Pascaline), Cornelis, F. (Franco̧is), Bignon, Y.-J. (Yves-Jean), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Maxwell, C.A. (Christopher), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Corines, M.J. (Marina J.), Villano, D. (Danylko), Cunningham, J.M. (Julie), Lee, A. (Adam), Lindor, N.M. (Noralane), Lázaro, C. (Conxi), Easton, D.F. (Douglas), Offit, K. (Kenneth), Chenevix-Trench, G. (Georgia), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis C.), and Pujana, M.A. (Miguel)
- Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appro
- Published
- 2015
- Full Text
- View/download PDF
13. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers
- Author
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Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, XS, Barrowdale, D, Garibay, GR, Librado, P, Sanchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Catala, I, Brunet, J, Feliubadalo, L, Tornero, E, Benitez, J, Osorio, A, Cajal, TRY, Nevanlinna, H, Aittomaki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Diez, O, Hansen, TV, Jonson, L, Gerdes, AM, Ejlertsen, B, de la Hoya, M, Caldees, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, Hogervorst, FBL, van der Hout, AH, Seynaeve, Caroline, van der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, van den Ouweland, Ans, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Gehrig, A, Bojesen, A, Pedersen, IS, Sunde, L, Jensen, UB, Thomassen, Marga, Kruse, TA, Foretova, L, Peterlongo, P, Bernard, L, Peissel, B, Scuvera, G, Manoukian, S, Radice, P, Ottini, L, Montagna, M, Agata, S, Maugard, C, Simard, J, Soucy, P, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Geschwantler-Kaulich, D, Tea, MK, Pfeiler, G, John, EM, Miron, A, Neuhausen, SL, Terry, MB, Chung, WK, Daly, MB, Goldgar, DE, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Fostira, F, Konstantopoulou, I, Garber, J, Godwin, AK, Olah, E, Narod, SA, Rennert, G, Paluch, SS, Laitman, Y, Friedman, E, Liljegren, A, Rantala, J, Stenmark-Askmalm, M, Loman, N, Imyanitov, EN, Hamann, U, Spurdle, AB, Healey, S, Weitzel, JN, Herzog, J, Margileth, D, Gorrini, C, Esteller, M, Gomez, A, Sayols, S, Vidal, E, Heyn, H, Stoppa-Lyonnet, Leone, M, Barjhoux, L, Fassy-Colcombet, M, de Pauw, A, Lasset, C, Ferrer, SF, Castera, L, Berthet, P, Cornelis, F, Bignon, YJ, Damiola, F, Mazoyer, S, Sinilnikova, OM, Maxwell, CA, Vijai, J, Robson, M, Kauff, N, Corines, MJ, Villano, D, Cunningham, J, van der Lee, A, Lindor, N, Lazaro, C (Conxi), Easton, DF, Offit, K, Chenevix-Trench, G, Couch, FJ, Antoniou, AC, Pujana, MA, Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, XS, Barrowdale, D, Garibay, GR, Librado, P, Sanchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Catala, I, Brunet, J, Feliubadalo, L, Tornero, E, Benitez, J, Osorio, A, Cajal, TRY, Nevanlinna, H, Aittomaki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Diez, O, Hansen, TV, Jonson, L, Gerdes, AM, Ejlertsen, B, de la Hoya, M, Caldees, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, Hogervorst, FBL, van der Hout, AH, Seynaeve, Caroline, van der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, van den Ouweland, Ans, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Gehrig, A, Bojesen, A, Pedersen, IS, Sunde, L, Jensen, UB, Thomassen, Marga, Kruse, TA, Foretova, L, Peterlongo, P, Bernard, L, Peissel, B, Scuvera, G, Manoukian, S, Radice, P, Ottini, L, Montagna, M, Agata, S, Maugard, C, Simard, J, Soucy, P, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Geschwantler-Kaulich, D, Tea, MK, Pfeiler, G, John, EM, Miron, A, Neuhausen, SL, Terry, MB, Chung, WK, Daly, MB, Goldgar, DE, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Fostira, F, Konstantopoulou, I, Garber, J, Godwin, AK, Olah, E, Narod, SA, Rennert, G, Paluch, SS, Laitman, Y, Friedman, E, Liljegren, A, Rantala, J, Stenmark-Askmalm, M, Loman, N, Imyanitov, EN, Hamann, U, Spurdle, AB, Healey, S, Weitzel, JN, Herzog, J, Margileth, D, Gorrini, C, Esteller, M, Gomez, A, Sayols, S, Vidal, E, Heyn, H, Stoppa-Lyonnet, Leone, M, Barjhoux, L, Fassy-Colcombet, M, de Pauw, A, Lasset, C, Ferrer, SF, Castera, L, Berthet, P, Cornelis, F, Bignon, YJ, Damiola, F, Mazoyer, S, Sinilnikova, OM, Maxwell, CA, Vijai, J, Robson, M, Kauff, N, Corines, MJ, Villano, D, Cunningham, J, van der Lee, A, Lindor, N, Lazaro, C (Conxi), Easton, DF, Offit, K, Chenevix-Trench, G, Couch, FJ, Antoniou, AC, and Pujana, MA
- Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
- Published
- 2015
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