Search

Your search keyword '"Küppers, Ralf"' showing total 963 results
Start Over Author "Küppers, Ralf"
963 results on '"Küppers, Ralf"'

157. Critical influences on the pathogenesis of follicular lymphoma

Author

Küppers, Ralf and Stevenson, Freda K

Abstract

The development of follicular lymphoma (FL) from a founder B cell with an upregulation of B-cell lymphoma 2 (BCL2), via the t(14;18) translocation, to a proliferating clone, poised to undergo further transformation to an aggressive lymphoma, illustrates the opportunistic Darwinian process of tumorigenesis. Protection against apoptosis allows an innocent cell to persist and divide, with dangerous accumulation of further mutational changes, commonly involving inactivation of chromatin-modifying genes. But this is not all. FL cells reflect normal B cells in relying on expression of surface immunoglobulin. In doing so, they add another supportive mechanism by exploiting the natural process of somatic hypermutation of the IGV genes. Positive selection of motifs for addition of glycan into the antigen-binding sites of virtually all cases, and the placement of unusual mannoses in those sites, reveals a posttranslational strategy to engage the microenvironment. A bridge between mannosylated surface immunoglobulin of FL cells and macrophage-expressed dendritic cell-specific ICAM-3-grabbing nonintegrin produces a persistent low-level signal that appears essential for life in the hostile germinal center. Early-stage FL therefore requires a triad of changes: protection from apoptosis, mutations in chromatin modifiers, and an ability to interact with lectin-expressing macrophages. These changes are common and persistent. Genetic/epigenetic analysis is providing important data but investigation of the posttranslational landscape is the next challenge. We have one glimpse of its operation via the influence of added glycan on the B-cell receptor of FL. The consequential interaction with environmental lectins illustrates how posttranslational modifications can be exploited by tumor cells, and could lead to new approaches to therapy.

Published
2018

158. IG‐MYC ‐positive leukemia and lymphoma with precursor B‐cell phenotype are genetically and epigenetically distinct from Burkitt lymphomas

Author

Lopez, Cristina, Wagener, Rabea, Kleinheinz, Kortine, Bausinger, Julia, Aukema, Sietse M., Nagel, Inga, Toprak, Umut H., Seufert, Julian, Altmueller, Janine, Thiele, Holger, Schneider, Christof, Kolarova, Julia, Park, Jeongbin, Hübschmann, Daniel, Penas, Eva M. Murga, Drexler, Hans G., Attarbaschi, Andishe, Hovland, Randi, Kjeldsen, Eigil, Kneba, Michael, Kontny, Udo, de Leval, Laurence, Nürnberg, Peter, Oschlies, Ilske, Oscier, David, Schlegelberger, Brigitte, Stilgenbauer, Stephan, Wössmann, Wilhelm, Schlesner, Matthias, Burkhardt, Birgit, Klapper, Wolfram, Jaffe, Elaine S., Küppers, Ralf, and Siebert, Reiner

Subjects
Medizin
Published
2018

160. The landscape of genomic alterations across childhood cancers

Author

Gröbner, Susanne N., Worst, Barbara C., Bender, Sebastian, Lichter, Peter, Jäger, Natalie, Buchhalter, Ivo, Korbel, Jan, Stütz, Adrian, Rausch, Tobias, Radlwimmer, Bernhard, Yaspo, Marie-Laure, Lehrach, Hans, Warnatz, Hans-Jörg, Hutter, Barbara, Landgraf, Pablo, Borkhardt, Arndt, Brors, Benedikt, Zapatka, Marc, Eils, Roland, Eils, Jürgen, Lawerenz, Christian, Siebert, Reiner, Wagner, Susanne, Sturm, Dominik, Haake, Andrea, Richter, Julia, Richter, Gesine, Lawerenz, Chris, Kerssemakers, Jules, Jaeger-Schmidt, Christina, Scholz, Ingrid, Bergmann, Anke K., Pfaff, Elke, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Dreyling, Martin, Eberth, Sonja, Einsele, Hermann, Frickhofen, Norbert, Haas, Siegfried, Hansmann, Martin-Leo, Karsch, Dennis, Hübschmann, Daniel, Kneba, Michael, Lisfeld, Jasmin, Mantovani-Löffler, Luisa, Rohde, Marius, Ott, German, Stadler, Christina, Staib, Peter, Stilgenbauer, Stephan, Trümper, Lorenz, Zenz, Thorsten, Zipprich, Gideon, Kube, Dieter, Küppers, Ralf, Weniger, Marc, Hummel, Michael, Klapper, Wolfram, Kostezka, Ulrike, Lenze, Dido, Möller, Peter, Rosenwald, Andreas, Heinold, Michael, Szczepanowski, Monika, Ammerpohl, Ole, Aukema, Sietse M., Binder, Vera, Hoell, Jessica I., Leich, Ellen, López, Cristina, Nagel, Inga, Pischimariov, Jordan, Rosenstiel, Philip, Schilhabel, Markus, Schreiber, Stefan, Vater, Inga, Wagener, Rabea, Bernhart, Stephan H., Binder, Hans, Doose, Gero, Hoffmann, Steve, Hopp, Lydia, Erkek, Serap, Kleinheinz, Kortine, Kretzmer, Helene, Kreuz, Markus, Langenberger, David, Loeffler, Markus, Rosolowski, Maciej, Schlesner, Matthias, Stadler, Peter F., Sungalee, Stephanie, Weischenfeldt, Joachim, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Hans Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Günther H., Schulte, Johannes, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, ICGC PedBrain-Seq Project, ICGC MMML-Seq Project, Rudneva, Vasilisa A., Kratz, Christian P., Witt, Olaf, van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Frühwald, Michael, von Hoff, Katja, Johann, Pascal D., Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Balasubramanian, Gnana Prakash, Zwijnenburg, Danny A., Raman, Pichai, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Segura-Wang, Maia, Jones, David T. W., Chavez, Lukas, Pfister, Stefan M., Weber, Ursula, Korshunov, Andrey, Brabetz, Sebastian, Pfister, Stefan, Reifenberger, Guido, Felsberg, Jörg, von Kalle, Christof, Schmidt, Manfred, Bartholomä, Cynthia, Taylor, Michael, and Jones, David

Published
2018

163. Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury

Author

Bankov, Katrin, primary, Döring, Claudia, additional, Ustaszewski, Adam, additional, Giefing, Maciej, additional, Herling, Marco, additional, Cencioni, Chiara, additional, Spallotta, Francesco, additional, Gaetano, Carlo, additional, Küppers, Ralf, additional, Hansmann, Martin-Leo, additional, and Hartmann, Sylvia, additional

Published
2019
Full Text
View/download PDF

164. MDM4 Is Targeted by 1q Gain and Drives Disease in Burkitt Lymphoma

Author

Hüllein, Jennifer, primary, Słabicki, Mikołaj, additional, Rosolowski, Maciej, additional, Jethwa, Alexander, additional, Habringer, Stefan, additional, Tomska, Katarzyna, additional, Kurilov, Roma, additional, Lu, Junyan, additional, Scheinost, Sebastian, additional, Wagener, Rabea, additional, Huang, Zhiqin, additional, Lukas, Marina, additional, Yavorska, Olena, additional, Helfrich, Hanne, additional, Scholtysik, René, additional, Bonneau, Kyle, additional, Tedesco, Donato, additional, Küppers, Ralf, additional, Klapper, Wolfram, additional, Pott, Christiane, additional, Stilgenbauer, Stephan, additional, Burkhardt, Birgit, additional, Löffler, Markus, additional, Trümper, Lorenz H., additional, Hummel, Michael, additional, Brors, Benedikt, additional, Zapatka, Marc, additional, Siebert, Reiner, additional, Kreuz, Markus, additional, Keller, Ulrich, additional, Huber, Wolfgang, additional, and Zenz, Thorsten, additional

Published
2019
Full Text
View/download PDF

167. Modeling of the Epigenome of the Cell-of-Origin Identifies Cancer-Specific DNA Methylation Patterns in CLL

Author

Wierzbinska, Justyna Anna, primary, Toth, Reka, additional, Ishaque, Naveed, additional, Mallm, Jan-Phillip, additional, Rippe, Karsten, additional, Mertens, Daniel, additional, Hielscher, Thomas, additional, Zenz, Thorsten, additional, Seifert, Marc, additional, Küppers, Ralf, additional, Assenov, Yassen, additional, Stilgenbauer, Stephan, additional, Byrd, John C., additional, Oakes, Christopher C., additional, Lipka, Daniel B., additional, and Plass, Christoph, additional

Published
2018
Full Text
View/download PDF

168. IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas

Author

Wagener, Rabea, primary, López, Cristina, primary, Kleinheinz, Kortine, primary, Bausinger, Julia, primary, Aukema, Sietse M., primary, Nagel, Inga, primary, Toprak, Umut H., primary, Seufert, Julian, primary, Altmüller, Janine, primary, Thiele, Holger, primary, Schneider, Christof, primary, Kolarova, Julia, primary, Park, Jeongbin, primary, Hübschmann, Daniel, primary, Murga Penas, Eva M., primary, Drexler, Hans G., primary, Attarbaschi, Andishe, primary, Hovland, Randi, primary, Kjeldsen, Eigil, primary, Kneba, Michael, primary, Kontny, Udo, primary, de Leval, Laurence, primary, Nürnberg, Peter, primary, Oschlies, Ilske, primary, Oscier, David, primary, Schlegelberger, Brigitte, primary, Stilgenbauer, Stephan, primary, Wössmann, Wilhelm, primary, Schlesner, Matthias, primary, Burkhardt, Birgit, primary, Klapper, Wolfram, primary, Jaffe, Elaine S., primary, Küppers, Ralf, primary, and Siebert, Reiner, primary

Published
2018
Full Text
View/download PDF

171. Ectopic expression of transcription factor BATF3 induces B-cell lymphomas in a murine B-cell transplantation model

Author

Weiser, Christian, Petkova, Mina, Rengstl, Benjamin, Döring, Claudia, Laer, Dorothee von, Hartmann, Sylvia, Küppers, Ralf, Hansmann, Martin-Leo, Newrzela, Sebastian, Weiser, Christian, Petkova, Mina, Rengstl, Benjamin, Döring, Claudia, Laer, Dorothee von, Hartmann, Sylvia, Küppers, Ralf, Hansmann, Martin-Leo, and Newrzela, Sebastian

Abstract

The mechanisms involved in malignant transformation of mature B and T lymphocytes are still poorly understood. In a previous study, we compared gene expression profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine zipper protein ATF-like 3 (BATF3) to be significantly upregulated in the tumor cells of both entities. To assess the oncogenic potential of BATF3 in lymphomagenesis and to dissect the molecular interactions of BATF3 in lymphoma cells, we retrovirally transduced murine mature T and B cells with a BATF3-encoding viral vector and transplanted each population into Rag1-deficient recipients. Intriguingly, BATF3-expressing B lymphocytes readily induced B-cell lymphomas after characteristic latencies, whereas T-cell transplanted animals remained healthy throughout the observation time. Further analyses revealed a germinal center B-cell-like phenotype of most BATF3-initiated lymphomas. In a multiple myeloma cell line, BATF3 inhibited BLIMP1 expression, potentially illuminating an oncogenic action of BATF3 in B-cell lymphomagenesis. In conclusion, BATF3 overexpression induces malignant transformation of mature B cells and might serve as a potential target in B-cell lymphoma treatment.

Published
2018

172. Quantitative Comparison of Abundance Structures of Generalized Communities: From B-Cell Receptor Repertoires to Microbiomes

Author

Saeedghalati, Mohammadkarim, Farahpour, Farnoush, Budeus, Bettina, Lange, Anja, Westendorf, Astrid M., Seifert, Marc, Küppers, Ralf, and Hoffmann, Daniel

Subjects
Entropy, Medizin, Quantitative Biology - Quantitative Methods, Immune Receptors, Biochemistry, Cellular types, B Cell Receptors, lcsh:QH301-705.5, Quantitative Methods (q-bio.QM), Data Management, Immune System Proteins, Ecology, Physics, Microbiota, Immune cells, Genomics, Fakultät für Biologie » Bioinformatics and Computational Biophysics, Community Ecology, Medical Microbiology, Physical Sciences, Thermodynamics, White blood cells, Forschungszentren » Center for Computational Sciences and Simulation (CCSS), Biologie, Research Article, Signal Transduction, Microbial Taxonomy, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Medizinische Mikrobiologie, Cell biology, Blood cells, Computer and Information Sciences, Ecological Metrics, Forschungszentren » Zentrum für Medizinische Biotechnologie (ZMB), Immunology, Microbial Genomics, Antibody-producing cells, Microbiology, Forschungszentren » Zentrum für Wasser- und Umweltforschung (ZWU), Medizinische Fakultät » Universitätsklinikum Essen » Institut für Zellbiologie (Tumorforschung), Genetics, ddc:61, Animals, Humans, Computer Simulation, ddc:610, Taxonomy, Medicine and health sciences, B cells, Models, Statistical, Models, Genetic, Ecology and Environmental Sciences, Biology and Life Sciences, Proteins, Genetic Variation, Species Diversity, Memory B cells, Genetics, Population, Animal cells, lcsh:Biology (General), FOS: Biological sciences, Microbiome, B-Cell Activation Factor Receptor
Abstract

The community, the assemblage of organisms co-existing in a given space and time, has the potential to become one of the unifying concepts of biology, especially with the advent of high-throughput sequencing experiments that reveal genetic diversity exhaustively. In this spirit we show that a tool from community ecology, the Rank Abundance Distribution (RAD), can be turned by the new MaxRank normalization method into a generic, expressive descriptor for quantitative comparison of communities in many areas of biology. To illustrate the versatility of the method, we analyze RADs from various generalized communities, i.e. assemblages of genetically diverse cells or organisms, including human B cells, gut microbiomes under antibiotic treatment and of different ages and countries of origin, and other human and environmental microbial communities. We show that normalized RADs enable novel quantitative approaches that help to understand structures and dynamics of complex generalized communities., Author Summary Living things are parts of complex communities, similar to humans living in cities. A quantitative way of describing such communities is to measure the abundance of each species in the community so that a sorted list of abundance numbers is produced, a so-called Rank Abundance Distribution (RAD). With recent breakthroughs in genome analysis this approach can also be applied to very complex communities, such as the community of the myriads of microbes in a human gut (gut microbiome), or the diverse set of human immune cells. One problem with this approach is that it is not trivial to quantitatively compare RADs for different communities, especially if they are highly complex. We show that it is possible to computationally “normalize” RADs so that they can be quantitatively compared across many different communities. In this way, this normalization enables insight into structures and dynamics of arbitrary communities. We demonstrate this with applications to human immune cells, gut microbiomes under antibiotic treatment or under different nutritional regimes, and environmental microbiomes.

Published
2017

175. Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocytepredominant Hodgkin lymphoma.

Author

Thurner, Lorenz, Hartmann, Sylvia, Fadle, Natalie, Regitz, Evi, Kemele, Maria, Yoo-Jin Kim, Bohle, Rainer Maria, Nimmesgern, Anna, von Müller, Lutz, Kempf, Volkhard A. J., Weniger, Marc A., Neumann, Frank, Schneider, Nadine, Vornanen, Martine, Sundström, Christer, de Leval, Laurence, Engert, Andreas, Eichenauer, Dennis A., Küppers, Ralf, and Preuss, Klaus-Dieter

Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta’ (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD+ LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD+ B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD+ DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and super-antigenic stimulation of B cells with RpoC-specific IgD+ BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

176. JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte-rich large B-cell lymphoma

Author

Schuhmacher, Bianca, primary, Bein, Julia, additional, Rausch, Tobias, additional, Benes, Vladimir, additional, Tousseyn, Thomas, additional, Vornanen, Martine, additional, Ponzoni, Maurilio, additional, Thurner, Lorenz, additional, Gascoyne, Randy, additional, Steidl, Christian, additional, Küppers, Ralf, additional, Hansmann, Martin-Leo, additional, and Hartmann, Sylvia, additional

Published
2018
Full Text
View/download PDF

182. TET2 mutations in B cells of patients affected by angioimmunoblastic T-cell lymphoma

Author

Schwartz, Friederike H., Cai, Qian, Fellmann, Eva, Hartmann, Sylvia, Mäyränpää, Mikko I., Karjalainen-Lindsberg, Marja-Liisa, Sundström, Christer, Scholtysik, René, Hansmann, Martin-Leo, Küppers, Ralf, Schwartz, Friederike H., Cai, Qian, Fellmann, Eva, Hartmann, Sylvia, Mäyränpää, Mikko I., Karjalainen-Lindsberg, Marja-Liisa, Sundström, Christer, Scholtysik, René, Hansmann, Martin-Leo, and Küppers, Ralf

Abstract

Angioimmunoblastic T-cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1(+) cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T-cell lymphoma clone. Thus, TET2-mutated haematopoietic precursor cells in AITL patients not only give rise to the T-cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B-cell lymphomas. Copyright (C) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2017
Full Text
View/download PDF

183. Alterations of miRNAs and miRNA-regulated mRNA expression in GC B cell lymphomas determined by integrative sequencing analysis

Author

Hezaveh, Kebria, Kloetgen, Andreas, Bernhart, Stephan H, Mahapatra, Kunal Das, Lenze, Dido, Richter, Julia, Haake, Andrea, Bergmann, Anke K, Brors, Benedikt, Burkhardt, Birgit, Claviez, Alexander, Drexler, Hans G, Eils, Roland, Haas, Siegfried, Hoffmann, Steve, Karsch, Dennis, Klapper, Wolfram, Kleinheinz, Kortine, Korbel, Jan, Kretzmer, Helene, Kreuz, Markus, Küppers, Ralf, Lawerenz, Chris, Leich, Ellen, Loeffler, Markus, Mantovani-Loeffler, Luisa, López, Cristina, McHardy, Alice C, Möller, Peter, Rohde, Marius, Rosenstiel, Philip, Rosenwald, Andreas, Schilhabel, Markus, Schlesner, Matthias, Scholz, Ingrid, Stadler, Peter F, Stilgenbauer, Stephan, Sungalee, Séphanie, Szczepanowski, Monika, Trümper, Lorenz, Weniger, Marc A, Siebert, Reiner, Borkhardt, Arndt, Hummel, Michael, Hoell, Jessica I, and Heinrich-Heine-University Duesseldorf, Medical Faculty, Department of Pediatric Oncology

Subjects
immune system diseases, hemic and lymphatic diseases
Abstract

MicroRNAs are well-established players in posttranscriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNAs/target mRNAs interaction is mostly lacking. Within the International Cancer Genome Consortium Project Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing (ICGC MMML-Seq), we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas. Twenty-two miRNAs separated Burkitt lymphomas from diffuse large B-cell lymphomas/follicular lymphomas, of which 13 have shown regulation by MYC. Moreover, we show expression of three hitherto unreported microRNAs. Additionally, we detect recurrent mutations of hsa-miR-142 in diffuse large B-cell lymphomas and follicular lymphomas, and editing of the hsa-miR-376 cluster, providing evidence for microRNA editing in lymphomagenesis. To interrogate the direct physical interactions of microRNAs with mRNAs, we performed Argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation experiments. MicroRNAs directly targeted 208 mRNAs in the Burkitt lymphomas and 328 mRNAs in the non-Burkitt lymphoma models. This integrative analysis discovered several regulatory pathways of relevance in lymphomagenesis including Ras, PI3K-Akt and MAPK signaling pathways, also recurrently deregulated in lymphomas by mutations. Our dataset uncovers in detail the mRNA deregulation through microRNAs as a highly relevant mechanism in lymphomagenesis.

Published
2016

185. Digital microfluidics for microchip-based cell sorting

Author

Kahnert, Stefan, Schreiber, Fedor, Goehlich, Andreas, Greifendorf, Dieter, Lennartz, Klaus, Kirstein, Uwe, Bartels, Frank, Janzyk, Udo, Rennings, Andreas, Erni, Daniel, Küppers, Ralf, and Vogt, Holger

Subjects
Medizin, Elektrotechnik
Published
2016

188. Efficient chip architectures for a microfluidic cell sorter actuated by electrowetting and its electro-hydrodynamic analysis

Author

Schreiber, Fedor, Kahnert, S., Goehlich, A., Greifendorf, D., Bartels, F., Janzyk, U., Lennartz, K., Kirstein, Uwe, Rennings, Andreas, Küppers, Ralf, and Erni, Daniel

Subjects
Hardware_INTEGRATEDCIRCUITS, Hardware_PERFORMANCEANDRELIABILITY, Hardware_ARITHMETICANDLOGICSTRUCTURES, Elektrotechnik
Abstract

We present the design and development of sorter architectures in conjunction with corresponding intelligent physical sorting algorithms for a chip-based microfluidic cell sorter actuated by the electrowetting on dielectric (EWOD) mechanism. This microfluidic chip realizes an implementation of FACS (fluorescence activated cell sorting), which operates on EWOD-manipulated droplets containing cells to be sorted. Poster Abstract

Published
2016

192. MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells

Author

Doose, Gero, Haake, Andrea, Bernhart, Stephan H., López, Cristina, Duggimpudi, Sujitha, Wojciech, Franziska, Bergmann, Anke K., Borkhardt, Arndt, Burkhardt, Birgit, Claviez, Alexander, Dimitrova, Lora, Haas, Siegfried, Hoell, Jessica I., Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kleo, Karsten, Kretzmer, Helene, Kreuz, Markus, Küppers, Ralf, Lawerenz, Chris, Lenze, Dido, Loeffler, Markus, Mantovani-Löffler, Luisa, Möller, Peter, Ott, German, Richter, Julia, Rohde, Marius, Rosenstiel, Philip, Rosenwald, Andreas, Schilhabel, Markus, Schneider, Markus, Scholz, Ingrid, Stilgenbauer, Stephan, Stunnenberg, Hendrik G., Szczepanowski, Monika, Trümper, Lorenz, Weniger, Marc A., Hoffmann, Steve, Siebert, Reiner, Iaccarino, Ingram, and Schlesner, Matthias

Subjects
Lymphoma, B-Cell, Cell Survival, Molecular Sequence Data, Medizin, MYC, Biology, Cell Line, Transcriptome, Proto-Oncogene Proteins c-myc, lncRNA, RNA interference, Cell Line, Tumor, Neoplasms, Sequence Homology, Nucleic Acid, Humans, Gene Regulatory Networks, ddc:610, Letters, RNA, Small Interfering, Promoter Regions, Genetic, Molecular Biology, Transcription factor, In Situ Hybridization, Fluorescence, Gene knockdown, Multidisciplinary, Binding Sites, Base Sequence, B-cell lymphoma, Gene Expression Profiling, Cell Cycle, Promoter, Cell cycle, Cell Cycle Gene, Molecular biology, Burkitt Lymphoma, Chromatin, Cell biology, Gene Expression Regulation, Neoplastic, PNAS Plus, RNA, Long Noncoding
Abstract

Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.

Published
2015

193. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma

Author

Mansouri, Larry, primary, Noerenberg, Daniel, additional, Young, Emma, additional, Mylonas, Elena, additional, Abdulla, Maysaa, additional, Frick, Mareike, additional, Asmar, Fazila, additional, Ljungström, Viktor, additional, Schneider, Markus, additional, Yoshida, Kenichi, additional, Skaftason, Aron, additional, Pandzic, Tatjana, additional, Gonzalez, Blanca, additional, Tasidou, Anna, additional, Waldhueter, Nils, additional, Rivas-Delgado, Alfredo, additional, Angelopoulou, Maria, additional, Ziepert, Marita, additional, Arends, Christopher Maximilian, additional, Couronné, Lucile, additional, Lenze, Dido, additional, Baldus, Claudia D., additional, Bastard, Christian, additional, Okosun, Jessica, additional, Fitzgibbon, Jude, additional, Dörken, Bernd, additional, Drexler, Hans G., additional, Roos-Weil, Damien, additional, Schmitt, Clemens A., additional, Munch-Petersen, Helga D., additional, Zenz, Thorsten, additional, Hansmann, Martin-Leo, additional, Strefford, Jonathan C., additional, Enblad, Gunilla, additional, Bernard, Olivier A., additional, Ralfkiaer, Elisabeth, additional, Erlanson, Martin, additional, Korkolopoulou, Penelope, additional, Hultdin, Magnus, additional, Papadaki, Theodora, additional, Grønbæk, Kirsten, additional, Lopez-Guillermo, Armando, additional, Ogawa, Seishi, additional, Küppers, Ralf, additional, Stamatopoulos, Kostas, additional, Stavroyianni, Niki, additional, Kanellis, George, additional, Rosenwald, Andreas, additional, Campo, Elias, additional, Amini, Rose-Marie, additional, Ott, German, additional, Vassilakopoulos, Theodoros P., additional, Hummel, Michael, additional, Rosenquist, Richard, additional, and Damm, Frederik, additional

Published
2016
Full Text
View/download PDF

195. The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery

Author

Stunnenberg, Hendrik G., primary, Hirst, Martin, additional, Abrignani, Sergio, additional, Adams, David, additional, de Almeida, Melanie, additional, Altucci, Lucia, additional, Amin, Viren, additional, Amit, Ido, additional, Antonarakis, Stylianos E., additional, Aparicio, Samuel, additional, Arima, Takahiro, additional, Arrigoni, Laura, additional, Arts, Rob, additional, Asnafi, Vahid, additional, Esteller, Manel, additional, Bae, Jae-Bum, additional, Bassler, Kevin, additional, Beck, Stephan, additional, Berkman, Benjamin, additional, Bernstein, Bradley E., additional, Bilenky, Mikhail, additional, Bird, Adrian, additional, Bock, Christoph, additional, Boehm, Bernhard, additional, Bourque, Guillaume, additional, Breeze, Charles E., additional, Brors, Benedikt, additional, Bujold, David, additional, Burren, Oliver, additional, Bussemakers, Marion J., additional, Butterworth, Adam, additional, Campo, Elias, additional, Carrillo-de-Santa-Pau, Enrique, additional, Chadwick, Lisa, additional, Chan, Kui Ming, additional, Chen, Wei, additional, Cheung, Tom H., additional, Chiapperino, Luca, additional, Choi, Nak Hyen, additional, Chung, Ho-Ryun, additional, Clarke, Laura, additional, Connors, Joseph M., additional, Cronet, Philippe, additional, Danesh, John, additional, Dermitzakis, Manolis, additional, Drewes, Gerard, additional, Durek, Pawel, additional, Dyke, Stephanie, additional, Dylag, Tomasz, additional, Eaves, Connie J., additional, Ebert, Peter, additional, Eils, Roland, additional, Eils, Jürgen, additional, Ennis, Catherine A., additional, Enver, Tariq, additional, Feingold, Elise A., additional, Felder, Bärbel, additional, Ferguson-Smith, Anne, additional, Fitzgibbon, Jude, additional, Flicek, Paul, additional, Foo, Roger S.-Y., additional, Fraser, Peter, additional, Frontini, Mattia, additional, Furlong, Eileen, additional, Gakkhar, Sitanshu, additional, Gasparoni, Nina, additional, Gasparoni, Gilles, additional, Geschwind, Daniel H., additional, Glažar, Petar, additional, Graf, Thomas, additional, Grosveld, Frank, additional, Guan, Xin-Yuan, additional, Guigo, Roderic, additional, Gut, Ivo G., additional, Hamann, Alf, additional, Han, Bok-Ghee, additional, Harris, R. Alan, additional, Heath, Simon, additional, Helin, Kristian, additional, Hengstler, Jan G., additional, Heravi-Moussavi, Alireza, additional, Herrup, Karl, additional, Hill, Steven, additional, Hilton, Jason A., additional, Hitz, Benjamin C., additional, Horsthemke, Bernhard, additional, Hu, Ming, additional, Hwang, Joo-Yeon, additional, Ip, Nancy Y., additional, Ito, Takashi, additional, Javierre, Biola-Maria, additional, Jenko, Sasa, additional, Jenuwein, Thomas, additional, Joly, Yann, additional, Jones, Steven J.M., additional, Kanai, Yae, additional, Kang, Hee Gyung, additional, Karsan, Aly, additional, Kiemer, Alexandra K., additional, Kim, Song Cheol, additional, Kim, Bong-Jo, additional, Kim, Hyeon-Hoe, additional, Kimura, Hiroshi, additional, Kinkley, Sarah, additional, Klironomos, Filippos, additional, Koh, In-Uk, additional, Kostadima, Myrto, additional, Kressler, Christopher, additional, Kreuzhuber, Roman, additional, Kundaje, Anshul, additional, Küppers, Ralf, additional, Larabell, Carolyn, additional, Lasko, Paul, additional, Lathrop, Mark, additional, Lee, Daniel H.S., additional, Lee, Suman, additional, Lehrach, Hans, additional, Leitão, Elsa, additional, Lengauer, Thomas, additional, Lernmark, Åke, additional, Leslie, R. David, additional, Leung, Gilberto K.K., additional, Leung, Danny, additional, Loeffler, Markus, additional, Ma, Yussanne, additional, Mai, Antonello, additional, Manke, Thomas, additional, Marcotte, Eric R., additional, Marra, Marco A., additional, Martens, Joost H.A., additional, Martin-Subero, Jose Ignacio, additional, Maschke, Karen, additional, Merten, Christoph, additional, Milosavljevic, Aleksandar, additional, Minucci, Saverio, additional, Mitsuyama, Totai, additional, Moore, Richard A., additional, Müller, Fabian, additional, Mungall, Andrew J., additional, Netea, Mihai G., additional, Nordström, Karl, additional, Norstedt, Irene, additional, Okae, Hiroaki, additional, Onuchic, Vitor, additional, Ouellette, Francis, additional, Ouwehand, Willem, additional, Pagani, Massimiliano, additional, Pancaldi, Vera, additional, Pap, Thomas, additional, Pastinen, Tomi, additional, Patel, Ronak, additional, Paul, Dirk S., additional, Pazin, Michael J., additional, Pelicci, Pier Giuseppe, additional, Phillips, Anthony G., additional, Polansky, Julia, additional, Porse, Bo, additional, Pospisilik, J. Andrew, additional, Prabhakar, Shyam, additional, Procaccini, Dena C., additional, Radbruch, Andreas, additional, Rajewsky, Nikolaus, additional, Rakyan, Vardham, additional, Reik, Wolf, additional, Ren, Bing, additional, Richardson, David, additional, Richter, Andreas, additional, Rico, Daniel, additional, Roberts, David J., additional, Rosenstiel, Philip, additional, Rothstein, Mark, additional, Salhab, Abdulrahman, additional, Sasaki, Hiroyuki, additional, Satterlee, John S., additional, Sauer, Sascha, additional, Schacht, Claudia, additional, Schmidt, Florian, additional, Schmitz, Gerd, additional, Schreiber, Stefan, additional, Schröder, Christopher, additional, Schübeler, Dirk, additional, Schultze, Joachim L., additional, Schulyer, Ronald P., additional, Schulz, Marcel, additional, Seifert, Martin, additional, Shirahige, Katsuhiko, additional, Siebert, Reiner, additional, Sierocinski, Thomas, additional, Siminoff, Laura, additional, Sinha, Anupam, additional, Soranzo, Nicole, additional, Spicuglia, Salvatore, additional, Spivakov, Mikhail, additional, Steidl, Christian, additional, Strattan, J. Seth, additional, Stratton, Michael, additional, Südbeck, Peter, additional, Sun, Hao, additional, Suzuki, Narumi, additional, Suzuki, Yutaka, additional, Tanay, Amos, additional, Torrents, David, additional, Tyson, Frederick L., additional, Ulas, Thomas, additional, Ullrich, Sebastian, additional, Ushijima, Toshikazu, additional, Valencia, Alfonso, additional, Vellenga, Edo, additional, Vingron, Martin, additional, Wallace, Chris, additional, Wallner, Stefan, additional, Walter, Jörn, additional, Wang, Huating, additional, Weber, Stephanie, additional, Weiler, Nina, additional, Weller, Andreas, additional, Weng, Andrew, additional, Wilder, Steven, additional, Wiseman, Sam M., additional, Wu, Angela R., additional, Wu, Zhenguo, additional, Xiong, Jieyi, additional, Yamashita, Yasuhiro, additional, Yang, Xinyi, additional, Yap, Desmond Y., additional, Yip, Kevin Y., additional, Yip, Stephen, additional, Yoo, Jae-Il, additional, Zerbino, Daniel, additional, and Zipprich, Gideon, additional

Published
2016
Full Text
View/download PDF

196. Additional file 8: Figure S2. of Whole exome sequencing of microdissected splenic marginal zone lymphoma: a study to discover novel tumor-specific mutations

Author

Peveling-Oberhag, Jan, Wolters, Franziska, Döring, Claudia, Walter, Dirk, Sellmann, Ludger, Scholtysik, René, Lucioni, Marco, Schubach, Max, Paulli, Marco, Biskup, Saskia, Zeuzem, Stefan, Küppers, Ralf, and Martin-Leo Hansmann

Subjects
endocrine system, endocrine system diseases
Abstract

Sanger validation of NOTCH2 p.Q2364* nonsense mutation. Nucleotide substitution c.7090C > T in the NOTCH2 PEST domain within exon 34. (DOC 263 kb)

Published
2015
Full Text
View/download PDF

197. Additional file 7: Figure S1. of Whole exome sequencing of microdissected splenic marginal zone lymphoma: a study to discover novel tumor-specific mutations

Author

Peveling-Oberhag, Jan, Wolters, Franziska, Döring, Claudia, Walter, Dirk, Sellmann, Ludger, Scholtysik, René, Lucioni, Marco, Schubach, Max, Paulli, Marco, Biskup, Saskia, Zeuzem, Stefan, Küppers, Ralf, and Martin-Leo Hansmann

Abstract

Pyrosequencing of validation cohort. Five genes with SNVs in the discovery cohort were analysed for recurrent mutations in a validation cohort (n = 24). Only the SNV position of the respective discovery case was analysed. A. MYD88 794 T > C. B. NOCTH2 7090C > T. C. SMYD1 836G > T. D. PDE10A 1072G > A. E. ZNF608 3659A > G. (DOC 291 kb)

Published
2015
Full Text
View/download PDF

198. Additional file 9: Figure S3. of Whole exome sequencing of microdissected splenic marginal zone lymphoma: a study to discover novel tumor-specific mutations

Author

Peveling-Oberhag, Jan, Wolters, Franziska, Döring, Claudia, Walter, Dirk, Sellmann, Ludger, Scholtysik, René, Lucioni, Marco, Schubach, Max, Paulli, Marco, Biskup, Saskia, Zeuzem, Stefan, Küppers, Ralf, and Martin-Leo Hansmann

Abstract

Crystalline structure of the murine SMYD1. Coding mutations found in SMZL are highlighted (c.836G > T; p.C279F in blue, c.962C > A; p.S321Y in red). (DOC 232 kb)

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results