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1. Genomic ALK alterations in primary and relapsed neuroblastoma

Author

Rosswog, Carolina, Fassunke, Jana, Ernst, Angela, Schömig-Markiefka, Birgid, Merkelbach-Bruse, Sabine, Bartenhagen, Christoph, Cartolano, Maria, Ackermann, Sandra, Theissen, Jessica, Blattner-Johnson, Mirjam, Jones, Barbara, Schramm, Kathrin, Altmüller, Janine, Nürnberg, Peter, Ortmann, Monika, Berthold, Frank, Peifer, Martin, Büttner, Reinhard, Westermann, Frank, Schulte, Johannes H., Simon, Thorsten, Hero, Barbara, and Fischer, Matthias

Published
2023
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2. A mechanistic classification of clinical phenotypes in neuroblastoma

Author

Ackermann, Sandra, Cartolano, Maria, Hero, Barbara, Welte, Anne, Kahlert, Yvonne, Roderwieser, Andrea, Bartenhagen, Christoph, Walter, Esther, Gecht, Judith, Kerschke, Laura, Volland, Ruth, Menon, Roopika, Heuckmann, Johannes M., Gartlgruber, Moritz, Hartlieb, Sabine, Henrich, Kai-Oliver, Okonechnikov, Konstantin, Altmüller, Janine, Nürnberg, Peter, Lefever, Steve, de Wilde, Bram, Sand, Frederik, Ikram, Fakhera, Rosswog, Carolina, Fischer, Janina, Theissen, Jessica, Hertwig, Falk, Singhi, Aatur D., Simon, Thorsten, Vogel, Wenzel, Perner, Sven, Krug, Barbara, Schmidt, Matthias, Rahmann, Sven, Achter, Viktor, Lang, Ulrich, Vokuhl, Christian, Ortmann, Monika, Büttner, Reinhard, Eggert, Angelika, Speleman, Frank, O’Sullivan, Roderick J., Thomas, Roman K., Berthold, Frank, Vandesompele, Jo, Schramm, Alexander, Westermann, Frank, Schulte, Johannes H., Peifer, Martin, and Fischer, Matthias

Published
2018

3. ATM activity in T cells is critical for immune surveillance of lymphoma in vivo

Author

Riabinska, Arina, Lehrmann, Daria, Jachimowicz, Ron Daniel, Knittel, Gero, Fritz, Christian, Schmitt, Anna, Geyer, Aenne, Heneweer, Carola, Wittersheim, Maike, Frenzel, Lukas P., Torgovnick, Alessandro, Wiederstein, Janica Lea, Wunderlich, Claudia Maria, Ortmann, Monika, Paillard, Arlette, Wößmann, Wilhelm, Borkhardt, Arndt, Burdach, Stefan, Hansmann, Martin-Leo, Rosenwald, Andreas, Perner, Sven, Mall, Gita, Klapper, Wolfram, Merseburg, Andrea, Krüger, Marcus, Grüll, Holger, Persigehl, Thorsten, Wunderlich, Frank Thomas, Peifer, Martin, Utermöhlen, Olaf, Büttner, Reinhard, Beleggia, Filippo, and Reinhardt, Hans Christian

Published
2020
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5. Table S2 from Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies

Author

Flümann, Ruth, primary, Hansen, Julia, primary, Pelzer, Benedikt W., primary, Nieper, Pascal, primary, Lohmann, Tim, primary, Kisis, Ilmars, primary, Riet, Tobias, primary, Kohlhas, Viktoria, primary, Nguyen, Phuong-Hien, primary, Peifer, Martin, primary, Abedpour, Nima, primary, Bosco, Graziella, primary, Thomas, Roman K., primary, Kochanek, Moritz, primary, Knüfer, Jacqueline, primary, Jonigkeit, Lorenz, primary, Beleggia, Filippo, primary, Holzem, Alessandra, primary, Büttner, Reinhard, primary, Lohneis, Philipp, primary, Meinel, Jörn, primary, Ortmann, Monika, primary, Persigehl, Thorsten, primary, Hallek, Michael, primary, Calado, Dinis Pedro, primary, Chmielewski, Markus, primary, Klein, Sebastian, primary, Göthert, Joachim R., primary, Chapuy, Bjoern, primary, Zevnik, Branko, primary, Wunderlich, F. Thomas, primary, von Tresckow, Bastian, primary, Jachimowicz, Ron D., primary, Melnick, Ari M., primary, Reinhardt, Hans Christian, primary, and Knittel, Gero, primary

Published
2023
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6. Supplementary Figures S1 to S12 from Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies

Author

Flümann, Ruth, primary, Hansen, Julia, primary, Pelzer, Benedikt W., primary, Nieper, Pascal, primary, Lohmann, Tim, primary, Kisis, Ilmars, primary, Riet, Tobias, primary, Kohlhas, Viktoria, primary, Nguyen, Phuong-Hien, primary, Peifer, Martin, primary, Abedpour, Nima, primary, Bosco, Graziella, primary, Thomas, Roman K., primary, Kochanek, Moritz, primary, Knüfer, Jacqueline, primary, Jonigkeit, Lorenz, primary, Beleggia, Filippo, primary, Holzem, Alessandra, primary, Büttner, Reinhard, primary, Lohneis, Philipp, primary, Meinel, Jörn, primary, Ortmann, Monika, primary, Persigehl, Thorsten, primary, Hallek, Michael, primary, Calado, Dinis Pedro, primary, Chmielewski, Markus, primary, Klein, Sebastian, primary, Göthert, Joachim R., primary, Chapuy, Bjoern, primary, Zevnik, Branko, primary, Wunderlich, F. Thomas, primary, von Tresckow, Bastian, primary, Jachimowicz, Ron D., primary, Melnick, Ari M., primary, Reinhardt, Hans Christian, primary, and Knittel, Gero, primary

Published
2023
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7. Data from Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies

Author

Flümann, Ruth, primary, Hansen, Julia, primary, Pelzer, Benedikt W., primary, Nieper, Pascal, primary, Lohmann, Tim, primary, Kisis, Ilmars, primary, Riet, Tobias, primary, Kohlhas, Viktoria, primary, Nguyen, Phuong-Hien, primary, Peifer, Martin, primary, Abedpour, Nima, primary, Bosco, Graziella, primary, Thomas, Roman K., primary, Kochanek, Moritz, primary, Knüfer, Jacqueline, primary, Jonigkeit, Lorenz, primary, Beleggia, Filippo, primary, Holzem, Alessandra, primary, Büttner, Reinhard, primary, Lohneis, Philipp, primary, Meinel, Jörn, primary, Ortmann, Monika, primary, Persigehl, Thorsten, primary, Hallek, Michael, primary, Calado, Dinis Pedro, primary, Chmielewski, Markus, primary, Klein, Sebastian, primary, Göthert, Joachim R., primary, Chapuy, Bjoern, primary, Zevnik, Branko, primary, Wunderlich, F. Thomas, primary, von Tresckow, Bastian, primary, Jachimowicz, Ron D., primary, Melnick, Ari M., primary, Reinhardt, Hans Christian, primary, and Knittel, Gero, primary

Published
2023
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8. Supplementary Table 2 from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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9. Supplementary Data 1 from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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10. Supplementary Table 3 from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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11. Supplementary Table 1 from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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12. Supplementary Table 4 from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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13. Supplementary Figure 1 from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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14. Legends to Supplementaries from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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15. Supplementary Data 2 from Revised Risk Estimation and Treatment Stratification of Low- and Intermediate-Risk Neuroblastoma Patients by Integrating Clinical and Molecular Prognostic Markers

Author

Oberthuer, André, primary, Juraeva, Dilafruz, primary, Hero, Barbara, primary, Volland, Ruth, primary, Sterz, Carolina, primary, Schmidt, Rene, primary, Faldum, Andreas, primary, Kahlert, Yvonne, primary, Engesser, Anne, primary, Asgharzadeh, Shahab, primary, Seeger, Robert, primary, Ohira, Miki, primary, Nakagawara, Akira, primary, Scaruffi, Paola, primary, Tonini, Gian Paolo, primary, Janoueix-Lerosey, Isabelle, primary, Delattre, Olivier, primary, Schleiermacher, Gudrun, primary, Vandesompele, Jo, primary, Speleman, Frank, primary, Noguera, Rosa, primary, Piqueras, Marta, primary, Bénard, Jean, primary, Valent, Alexander, primary, Avigad, Smadar, primary, Yaniv, Isaac, primary, Grundy, Richard G., primary, Ortmann, Monika, primary, Shao, Chunxuan, primary, Schwab, Manfred, primary, Eils, Roland, primary, Simon, Thorsten, primary, Theissen, Jessica, primary, Berthold, Frank, primary, Westermann, Frank, primary, Brors, Benedikt, primary, and Fischer, Matthias, primary

Published
2023
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16. B-cell–specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice

Author

Knittel, Gero, Liedgens, Paul, Korovkina, Darya, Seeger, Jens M., Al-Baldawi, Yussor, Al-Maarri, Mona, Fritz, Christian, Vlantis, Katerina, Bezhanova, Svetlana, Scheel, Andreas H., Wolz, Olaf-Oliver, Reimann, Maurice, Möller, Peter, López, Cristina, Schlesner, Matthias, Lohneis, Philipp, Weber, Alexander N.R., Trümper, Lorenz, Staudt, Louis M., Ortmann, Monika, Pasparakis, Manolis, Siebert, Reiner, Schmitt, Clemens A., Klatt, Andreas R., Wunderlich, F.Thomas, Schäfer, Stephan C., Persigehl, Thorsten, Montesinos-Rongen, Manuel, Odenthal, Margarete, Büttner, Reinhard, Frenzel, Lukas P., Kashkar, Hamid, and Reinhardt, H.Christian

Published
2016
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17. Distinct genetically determined origins of Myd88/Bcl2-driven aggressive lymphoma rationalize targeted therapeutic intervention strategies

Author

Flümann, Ruth, Hansen, Julia, Pelzer, Benedikt W, Nieper, Pascal, Lohmann, Tim, Kisis, Ilmars, Riet, Tobias, Kohlhas, Viktoria, Nguyen, Phuong-Hien, Peifer, Martin, Abedpour, Nima, Bosco, Graziella, Thomas, Roman K, Kochanek, Moritz, Knüfer, Jacqueline, Jonigkeit, Lorenz, Beleggia, Filippo, Holzem, Alessandra, Büttner, Reinhard, Lohneis, Philipp, Meinel, Jörn, Ortmann, Monika, Persigehl, Thorsten, Hallek, Michael, Calado, Dinis Pedro, Chmielewski, Markus, Klein, Sebastian, Göthert, Joachim R, Chapuy, Bjoern, Zevnik, Branko, Wunderlich, F Thomas, von Tresckow, Bastian, Jachimowicz, Ron D, Melnick, Ari M, Reinhardt, Hans Christian, and Knittel, Gero

Subjects
Model organisms, Chemical Biology & High Throughput, Signalling & Oncogenes, Stem Cells, FOS: Clinical medicine, Immunology, Tumour Biology, Genetics & Genomics, Developmental Biology
Abstract

Genomic profiling revealed the identity of at least 5 subtypes of DLBCL, including the MCD/C5 cluster characterized by aberrations in MYD88, BCL2, PRDM1 and/or SPIB. We generated mouse models harboring B cell-specific Prdm1 or Spib aberrations on the background of oncogenic Myd88 and Bcl2 lesions. We deployed whole exome sequencing, transcriptome, flow- and mass cytometry analyses to demonstrate that Prdm1- or Spib-altered lymphomas display molecular features consistent with pre-memory B cells and light zone B cells, whereas lymphomas lacking these alterations were enriched for late light-zone and plasmablast-associated gene sets. Consistent with the phenotypic evidence for increased B cell receptor signaling activity in Prdm1-altered lymphomas, we demonstrate that combined BTK/BCL2 inhibition displays therapeutic activity in mice and in five out of six relapsed/refractory DLBCL patients. Moreover, Prdm1-altered lymphomas were immunogenic upon transplantation into immuno-competent hosts, displayed an actionable PD-L1 surface expression and were sensitive to anti-murine-CD19-CAR-T cell therapy, in vivo.

Published
2023
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18. Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies

Author

Flümann, Ruth, primary, Hansen, Julia, additional, Pelzer, Benedikt W., additional, Nieper, Pascal, additional, Lohmann, Tim, additional, Kisis, Ilmars, additional, Riet, Tobias, additional, Kohlhas, Viktoria, additional, Nguyen, Phuong-Hien, additional, Peifer, Martin, additional, Abedpour, Nima, additional, Bosco, Graziella, additional, Thomas, Roman K., additional, Kochanek, Moritz, additional, Knüfer, Jacqueline, additional, Jonigkeit, Lorenz, additional, Beleggia, Filippo, additional, Holzem, Alessandra, additional, Büttner, Reinhard, additional, Lohneis, Philipp, additional, Meinel, Jörn, additional, Ortmann, Monika, additional, Persigehl, Thorsten, additional, Hallek, Michael, additional, Calado, Dinis Pedro, additional, Chmielewski, Markus, additional, Klein, Sebastian, additional, Göthert, Joachim R., additional, Chapuy, Bjoern, additional, Zevnik, Branko, additional, Wunderlich, F. Thomas, additional, von Tresckow, Bastian, additional, Jachimowicz, Ron D., additional, Melnick, Ari M., additional, Reinhardt, Hans Christian, additional, and Knittel, Gero, additional

Published
2022
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21. Two mouse models reveal an actionable PARP1 dependence in aggressive chronic lymphocytic leukemia

Author

Knittel, Gero, Rehkämper, Tim, Korovkina, Darya, Liedgens, Paul, Fritz, Christian, Torgovnick, Alessandro, Al-Baldawi, Yussor, Al-Maarri, Mona, Cun, Yupeng, Fedorchenko, Oleg, Riabinska, Arina, Beleggia, Filippo, Nguyen, Phuong-Hien, Wunderlich, F. Thomas, Ortmann, Monika, Montesinos-Rongen, Manuel, Tausch, Eugen, Stilgenbauer, Stephan, P. Frenzel, Lukas, Herling, Marco, Herling, Carmen, Bahlo, Jasmin, Hallek, Michael, Peifer, Martin, Buettner, Reinhard, Persigehl, Thorsten, and Reinhardt, H. Christian

Published
2017
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25. Phenotype Discordance between Primary Tumor and Metastasis Impacts Metastasis Site and Outcome: Results of WSG-DETECT-PriMet

Author

Kolberg-Liedtke, Cornelia, primary, Wuerstlein, Rachel, additional, Gluz, Oleg, additional, Heitz, Florian, additional, Freudenberger, Muriel, additional, Bensmann, Elena, additional, du Bois, Andreas, additional, Nitz, Ulrike, additional, Pelz, Enrico, additional, Warm, Matthias, additional, Ortmann, Monika, additional, Sultova, Elena, additional, Brucker, Sara Y., additional, Kates, Ronald E., additional, Fehm, Tanja, additional, and Harbeck, Nadia, additional

Published
2020
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26. Telomerase Is a Prognostic Marker of Poor Outcome and a Therapeutic Target in Neuroblastoma

Author

Roderwieser, Andrea, primary, Sand, Frederik, additional, Walter, Esther, additional, Fischer, Janina, additional, Gecht, Judith, additional, Bartenhagen, Christoph, additional, Ackermann, Sandra, additional, Otte, Felix, additional, Welte, Anne, additional, Kahlert, Yvonne, additional, Lieberz, Daniela, additional, Hertwig, Falk, additional, Reinhardt, H. Christian, additional, Simon, Thorsten, additional, Peifer, Martin, additional, Ortmann, Monika, additional, Büttner, Reinhard, additional, Hero, Barbara, additional, O’Sullivan, Roderick J., additional, Berthold, Frank, additional, and Fischer, Matthias, additional

Published
2019
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27. ATM activity in T cells is critical for immune surveillance of lymphoma in vivo

Author

Riabinska, Arina, primary, Lehrmann, Daria, additional, Jachimowicz, Ron Daniel, additional, Knittel, Gero, additional, Fritz, Christian, additional, Schmitt, Anna, additional, Geyer, Aenne, additional, Heneweer, Carola, additional, Wittersheim, Maike, additional, Frenzel, Lukas P., additional, Torgovnick, Alessandro, additional, Wiederstein, Janica Lea, additional, Wunderlich, Claudia Maria, additional, Ortmann, Monika, additional, Paillard, Arlette, additional, Wößmann, Wilhelm, additional, Borkhardt, Arndt, additional, Burdach, Stefan, additional, Hansmann, Martin-Leo, additional, Rosenwald, Andreas, additional, Perner, Sven, additional, Mall, Gita, additional, Klapper, Wolfram, additional, Merseburg, Andrea, additional, Krüger, Marcus, additional, Grüll, Holger, additional, Persigehl, Thorsten, additional, Wunderlich, Frank Thomas, additional, Peifer, Martin, additional, Utermöhlen, Olaf, additional, Büttner, Reinhard, additional, Beleggia, Filippo, additional, and Reinhardt, Hans Christian, additional

Published
2019
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28. Telomerase Is a Prognostic Marker of Poor Outcome and a Therapeuctic Target in Neuroblastoma

Author

Roderwieser, Andrea, Sand, Frederik, Walter, Esther, Fischer, Janina, Gecht, Judith, Bartenhagen, Christoph, Ackermann, Sandra, Otte, Felix, Welte, Anne, Kahlert, Yvonne, Lieberz, Daniela, Hertwig, Falk, Reinhardt, H. Christian, Simon, Thorsten, Peifer, Martin, Ortmann, Monika, Buettner, Reinhard, Hero, Barbara, O'Sullivan, Roderick J., Berthold, Frank, Fischer, Matthias, Roderwieser, Andrea, Sand, Frederik, Walter, Esther, Fischer, Janina, Gecht, Judith, Bartenhagen, Christoph, Ackermann, Sandra, Otte, Felix, Welte, Anne, Kahlert, Yvonne, Lieberz, Daniela, Hertwig, Falk, Reinhardt, H. Christian, Simon, Thorsten, Peifer, Martin, Ortmann, Monika, Buettner, Reinhard, Hero, Barbara, O'Sullivan, Roderick J., Berthold, Frank, and Fischer, Matthias

Abstract

PURPOSE Telomere maintenance is a hallmark of high-risk neuroblastoma; however, the contribution of telomerase and alternative lengthening of telomeres (ALT) to clinical phenotypes has remained unclear. We aimed to determine the clinical relevance of telomerase activation versus ALT as biomarkers in pretreatment neuroblastoma and to assess the potential value of telomerase as a therapeutic target. MATERIALS AND METHODS The genomic status of TERT and MYCN was assessed in 457 pretreatment neuroblastomas by fluorescence in situ hybridization. ALT was examined in 273 of 457 tumors by detection of ALT-associated promyelocytic leukemia nuclear bodies, and TERT expression was determined by microarrays in 223 of these. Cytotoxic effects of telomerase-interacting compounds were analyzed in neuroblastoma cell lines in vitro and in vivo. RESULTS We detected TERT rearrangements in 46 of 457 cases (10.1%), MYCN amplification in 93 of 457 cases (20.4%), and elevated TERT expression in tumors lacking TERT or MYCN alterations in 10 of 223 cases (4.5%). ALT activation was found in 49 of 273 cases (17.9%). All these alterations occurred almost mutually exclusively and were associated with unfavorable prognostic variables and adverse outcome. The presence of activated telomerase (ie, TERT rearrangements, MYCN amplification, or high TERT expression without these alterations) was associated with poorest overall survival and was an independent prognostic marker in multi-variable analyses. We also found that the telomerase-interacting compound 6-thio-2'-deoxyguanosine effectively inhibited viability and proliferation of neuroblastoma cells bearing activated telomerase. Similarly, tumor growth was strongly impaired upon 6-thio-2'-deoxyguanosine treatment in telomerase-positive neuroblastoma xenografts in mice. CONCLUSION Our data suggest telomerase activation and ALT define distinct neuroblastoma subgroups with adverse outcome and that telomerase may represent a promising therapeutic targe

Published
2019

31. Phenotype Discordance between Primary Tumor and Metastasis Impacts Metastasis Site and Outcome: Results of WSG-DETECT-PriMet.

Author

Kolberg-Liedtke, Cornelia, Wuerstlein, Rachel, Gluz, Oleg, Heitz, Florian, Freudenberger, Muriel, Bensmann, Elena, du Bois, Andreas, Nitz, Ulrike, Pelz, Enrico, Warm, Matthias, Ortmann, Monika, Sultova, Elena, Brucker, Sara Y., Kates, Ronald E., Fehm, Tanja, and Harbeck, Nadia

Subjects
BREAST cancer prognosis, ONCOGENES, METASTASIS, CELL receptors, LYMPH nodes, RETROSPECTIVE studies, CANCER relapse, COMPARATIVE studies, CANCER patients, SURVIVAL analysis (Biometry), DESCRIPTIVE statistics, PHENOTYPES, BREAST tumors, HORMONE receptor positive breast cancer, LONGITUDINAL method, TUMOR grading
Abstract

Introduction: Tumor biological factors of breast cancer (BC) such as hormone receptor (HR) status, HER2 status, and grade can differ in the metastatic cascade from primary to lymph node (LN) metastasis and to distant metastatic tissue. Systematic data regarding therapeutic consequences are yet limited. Methods: We conducted a prospectively planned, retrospective cohort study comparing BC phenotype in tissue from primary tumors (PTs), locoregional LN metastases, and disease recurrence (DR). HR and HER2 as well as tumor grade in PTs and DR were obtained by a database search. No centralized biomarker testing was performed. The impact of changes in tumor biological factors on post-recurrence survival (PRS) and overall survival was analyzed. Results: PriMet comprises 635 patients (LN tissue in 142 patients). Discrepancies for HR or HER2 status between PT and DR were observed in 18.7 and 21.6% of cases, respectively. For HR status, positivity of PT and negativity of DR was seen more often (13.2%) than vice versa (5.5%). For HER2 status, negativity of the primary and positivity of DR was seen more often (14.9%) than vice versa (6.7%). Discordance was more often observed between PT and LN metastasis compared to LN versus DR. However, numbers were small. Compared to concordant non-triple-negative (TN) disease, concordant TN disease showed significantly inferior PRS. Conclusion: We demonstrate receptor discordance to occur relatively frequently between PT, LN metastasis, and DR and to impact patient prognosis. However, clinical consequences of receptor discordance need to be drawn with caution considering clinical aspects as well as tumor biology. [ABSTRACT FROM AUTHOR]

Published
2021
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35. Uveal Melanoma Cell Seeding after Transretinal Tumor Biopsy?

Author

Koch, Konrad R., Hishmi, Ahmed M., Ortmann, Monika, Heindl, Ludwig M., Koch, Konrad R., Hishmi, Ahmed M., Ortmann, Monika, and Heindl, Ludwig M.

Abstract

Background/Aims: To report a case and the histopathology of uveal melanoma cell seeding following transretinal tumor biopsy for a suspected uveal lesion. Methods: Interventional case report. Results: A 66-year-old male presented with a pigmented perilimbal episcleral lesion overlying an intraocular mass at the pars plana, 3.5 years after transretinal biopsy and ruthenium plaque brachytherapy for a choroidal melanoma at the posterior pole. The patient underwent enucleation of the eye. Histopathology confirmed a recurrence of uveal melanoma with intra-and extrascleral tumor portions. Serial sections revealed the posterior border of this newfound pars plana melanoma separated from the radiation scar by a viable and tumor-free choroidal area, thus failing to establish a continuity between secondary and primary tumor. Conclusion: Transretinal tumor biopsy is of high diagnostic and prognostic value in the management of uveal lesions, but also bears the potential risk for tumor cell seeding. (C) 2017 S. Karger AG, Basel

Published
2017

36. Discordance and Conversion Rates of Progesterone-, Estrogen-, and HER2/neu-Receptor Status in Primary Breast Cancer and Brain Metastasis Mainly Triggered by Hormone Therapy

Author

Timmer, Marco, Werner, Jan-Michael, Roehn, Gabriele, Ortmann, Monika, Blau, Tobias, Cramer, Christina, Stavrinou, Pantelis, Krischek, Boris, Mallman, Peter, Goldbrunner, Roland, Timmer, Marco, Werner, Jan-Michael, Roehn, Gabriele, Ortmann, Monika, Blau, Tobias, Cramer, Christina, Stavrinou, Pantelis, Krischek, Boris, Mallman, Peter, and Goldbrunner, Roland

Abstract

Background/Aim: Knowing the molecular footprint of tumors is a precondition for personalized medicine. For breast cancer, targeted therapies are frequently based on the molecular status of the tissue gained from the primary tumor operation. However, it is unclear whether metastases in different organs maintain the same status. Patients and Methods: We compared the estrogen-(ER), progesterone-(PgR) and HER2/neu receptor status of the primary tumor with brain metastases in a series of 24 consecutive breast cancer patients. Results: 62.5-75% of patients exhibited a constant receptor status between the primary tumor and the brain metastasis, whereas discordance rates of 25-37.5% were found, depending on the receptor. The rate of ER and PgR expression was each 41.6% in the primary tumors and decreased to 12.5% and 16.6% in the brain metastases. In contrast, the rate for Her2+ tumors increased from 41.6% in primary breast cancer to 65.2% in the respective brain metastases. The Ki-67 proliferation index increased significantly from a mean of 21% at the primary tumor site to 60% in brain metastases (p<0.001). All anti-estrogen treated breast tumors lost the estrogen receptor expression in the brain metastases, whereas no Her2/neu conversions occurred after treatment with trastuzumab. Conclusion: In summary, receptor conversion is frequent during disease progression. Therefore, the receptor status of the primary tumor is invalid for planning a therapy targeted against brain metastases, especially after hormone-therapy. In these cases, new tissue collection by biopsy or resection is mandatory for the selection of adequate therapeutic targets and accurate decision-making for systemic therapies.

Published
2017

39. Schulpädagogisches Coping angesichts progredient erkrankter Kinder und Jugendlicher – zum pädagogischen Umgang mit Tod, Sterben und Trauer in der Schule

Author

Ortmann, Monika, Jennessen, Sven, Bruns, Christian, and Uhrlau, Katrin

Subjects
Social problems, social services, insurance, Education
Abstract

Kinder und Jugendliche mit chronischen und progredienten Erkrankungen sind in allen Schulformen anzutreffen, insbesondere werden sie aber durch Förderzentren für Kinder und Jugendliche mit körperlichen Beeinträchtigungen schulisch betreut sowie in Sonderschulen für Körperbehinderte unterrichtet. Die Schule für Körperbehinderte ist häufig der geeignete Lern- und Lebensort für Kinder und Jugendliche mit eingeschränkter Lebenserwartung. In dieser Schulform kann dieser Schülerschaft besondere Aufmerksamkeit gewidmet werden. Im Rahmen der richtungsweisenden Lehrpläne können bedürfnisorientiert veränderte didaktische Schwerpunkte gesetzt werden. Die sonderpädagogische Förderung kann darüber hinaus durch physiotherapeutische, sozialpädagogische und pflegerische Maßnahmen sinnvoll ergänzt werden. Lehrkräfte dieser Schulform werden im Rahmen ihrer Berufstätigkeit häufig mehrfach mit der schwierigen Aufgabe konfrontiert, sich mit schwersten, progressiven Erkrankungen der Schülerinnen und Schüler, dem damit verbundenen Leid und mit dem Sterben auseinanderzusetzen.

Published
2014

40. Squamous Cell Carcinoma of the Pancreas in a Patient with Germline BRCA2 Mutation-Response to Neoadjuvant Radiochemotherapy

Author

Schultheis, Anne M., Nguyen, Gia Phuong, Ortmann, Monika, Kruis, Wolfgang, Büttner, Reinhard, Schildhaus, Hans-Ulrich, and Markiefka, Birgid

Subjects
Article Subject
Abstract

Primary squamous cell carcinoma of the pancreas is a rare malignant neoplasia, accounting for approximately 0.5–2% of all malignant pancreatic tumors. These lesions are characterized by poor prognosis. Here we report on a case of a 57-year-old female patient with known BRCA2 germline mutation presenting with primary squamous cell carcinoma of the pancreas as the only malignancy. The tumor was locally advanced at the first presentation but responded almost completely to neoadjuvant radio-chemotherapy. Our case highlights the facts (i) that pancreatic carcinomas belong to the tumor spectrum of patients with the BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) and (ii) that tumors of the pancreas can represent the first or even the only manifestation of HBOC. Furthermore, this case of a nonkeratinizing squamous cell carcinoma indicates that HBOC-associated carcinomas of the pancreas might be characterized by a broader morphological spectrum than was previously thought. Since BRCA mutations cause deficiency of DNA double-strand breakage repair in tumors, neoadjuvant treatment regimens might become a reasonable option in HBOC-associated pancreatic carcinomas. To our knowledge, this is the first reported case of a primary pancreatic squamous cell carcinoma in a patient with this particular genetic background of BRCA2-associated HBOC.

Published
2014
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42. Immunohistochemical Analysis of Cytochrome c Oxidase Facilitates Differentiation Between Oncocytoma and Chromophobe Renal Cell Carcinoma

Author

Adam, Alexander C., Scriba, Alexander, Ortmann, Monika, Huss, Sebastian, Kahl, Philip, Steiner, Susanne, Stoerkel, Stephan, Buettner, Reinhard, Adam, Alexander C., Scriba, Alexander, Ortmann, Monika, Huss, Sebastian, Kahl, Philip, Steiner, Susanne, Stoerkel, Stephan, and Buettner, Reinhard

Abstract

In this study, immunohistochemical staining pattern of cytochrome c oxidase subunit 1 (CCO1) was investigated in the differentiation of renal oncocytoma (RO) from eosinophilic (EoC) and classic chromophobe renal cell carcinoma (ChRCC). A feature found in ChRCC/EoC but not in RO is the predominance of a perinuclear halo when stained for CCO1. In a cohort of 103 mixed cases including 44 RO, 37 classic ChRCC and 22 EoC, the diagnosis based on this immunohistochemical feature alone was consistent with the previous routine diagnosis in 95.7%. We reached 100% specificity and 81.4% sensitivity of this pattern in ChRCC. Specificity for RO was 93.2% and sensitivity correspondingly 95.5%. We propose a novel and easily interpretable immunohistochemical method for the discrimination of benign RO from certain subtypes of malignant ChRCC. Because of strong similarity in morphology of the 2 entities the diagnosis often cannot be made based on standard histopathology alone. The study describes for the first time the formation of a perinuclear halo in CCO1 immunohistochemistry as a highly specific marker for the diagnosis of ChRCC. We think this method can be a strong amendment for routine diagnostics in renal cell carcinoma.

Published
2015

43. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

Author

Peifer, Martin, Hertwig, Falk, Roels, Frederik, Dreidax, Daniel, Gartlgruber, Moritz, Menon, Roopika, Kraemer, Andrea, Roncaioli, Justin L., Sand, Frederik, Heuckmann, Johannes M., Ikram, Fakhera, Schmidt, Rene, Ackermann, Sandra, Engesser, Anne, Kahlert, Yvonne, Vogel, Wenzel, Altmueller, Janine, Nuernberg, Peter, Thierry-Mieg, Jean, Thierry-Mieg, Danielle, Mariappan, Aruljothi, Heynck, Stefanie, Mariotti, Erika, Henrich, Kai-Oliver, Gloeckner, Christian, Bosco, Graziella, Leuschner, Ivo, Schweiger, Michal R., Savelyeva, Larissa, Watkins, Simon C., Shao, Chunxuan, Bell, Emma, Hoefer, Thomas, Achter, Viktor, Lang, Ulrich, Theissen, Jessica, Volland, Ruth, Saadati, Maral, Eggert, Angelika, de Wilde, Bram, Berthold, Frank, Peng, Zhiyu, Zhao, Chen, Shi, Leming, Ortmann, Monika, Buettner, Reinhard, Perner, Sven, Hero, Barbara, Schramm, Alexander, Schulte, Johannes H., Herrmann, Carl, O'Sullivan, Roderick J., Westermann, Frank, Thomas, Roman K., Fischer, Matthias, Peifer, Martin, Hertwig, Falk, Roels, Frederik, Dreidax, Daniel, Gartlgruber, Moritz, Menon, Roopika, Kraemer, Andrea, Roncaioli, Justin L., Sand, Frederik, Heuckmann, Johannes M., Ikram, Fakhera, Schmidt, Rene, Ackermann, Sandra, Engesser, Anne, Kahlert, Yvonne, Vogel, Wenzel, Altmueller, Janine, Nuernberg, Peter, Thierry-Mieg, Jean, Thierry-Mieg, Danielle, Mariappan, Aruljothi, Heynck, Stefanie, Mariotti, Erika, Henrich, Kai-Oliver, Gloeckner, Christian, Bosco, Graziella, Leuschner, Ivo, Schweiger, Michal R., Savelyeva, Larissa, Watkins, Simon C., Shao, Chunxuan, Bell, Emma, Hoefer, Thomas, Achter, Viktor, Lang, Ulrich, Theissen, Jessica, Volland, Ruth, Saadati, Maral, Eggert, Angelika, de Wilde, Bram, Berthold, Frank, Peng, Zhiyu, Zhao, Chen, Shi, Leming, Ortmann, Monika, Buettner, Reinhard, Perner, Sven, Hero, Barbara, Schramm, Alexander, Schulte, Johannes H., Herrmann, Carl, O'Sullivan, Roderick J., Westermann, Frank, Thomas, Roman K., and Fischer, Matthias

Abstract

Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system(1). Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive(2-4). Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type(1,2,5). In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.

Published
2015

44. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

Author

Peifer, Martin, primary, Hertwig, Falk, additional, Roels, Frederik, additional, Dreidax, Daniel, additional, Gartlgruber, Moritz, additional, Menon, Roopika, additional, Krämer, Andrea, additional, Roncaioli, Justin L., additional, Sand, Frederik, additional, Heuckmann, Johannes M., additional, Ikram, Fakhera, additional, Schmidt, Rene, additional, Ackermann, Sandra, additional, Engesser, Anne, additional, Kahlert, Yvonne, additional, Vogel, Wenzel, additional, Altmüller, Janine, additional, Nürnberg, Peter, additional, Thierry-Mieg, Jean, additional, Thierry-Mieg, Danielle, additional, Mariappan, Aruljothi, additional, Heynck, Stefanie, additional, Mariotti, Erika, additional, Henrich, Kai-Oliver, additional, Gloeckner, Christian, additional, Bosco, Graziella, additional, Leuschner, Ivo, additional, Schweiger, Michal R., additional, Savelyeva, Larissa, additional, Watkins, Simon C., additional, Shao, Chunxuan, additional, Bell, Emma, additional, Höfer, Thomas, additional, Achter, Viktor, additional, Lang, Ulrich, additional, Theissen, Jessica, additional, Volland, Ruth, additional, Saadati, Maral, additional, Eggert, Angelika, additional, de Wilde, Bram, additional, Berthold, Frank, additional, Peng, Zhiyu, additional, Zhao, Chen, additional, Shi, Leming, additional, Ortmann, Monika, additional, Büttner, Reinhard, additional, Perner, Sven, additional, Hero, Barbara, additional, Schramm, Alexander, additional, Schulte, Johannes H., additional, Herrmann, Carl, additional, O’Sullivan, Roderick J., additional, Westermann, Frank, additional, Thomas, Roman K., additional, and Fischer, Matthias, additional

Published
2015
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45. Changes in the Progesterone-, Estrogen-, HER2/neu-receptor status and the proliferation marker Ki-67 in metastasizing breast cancer: discordance rates and time to progression in brain metastases

Author

Cramer, Christina, Röhn, Gabriele, Ortmann, Monika, Goldbrunner, Roland, and Timmer, Marco

Subjects
breast cancer, ddc: 610, brain metastasis, hormone receptor, 610 Medical sciences, Medicine, skin and connective tissue diseases, hormones, hormone substitutes, and hormone antagonists
Abstract

Objective: Estrogen receptor (ER), progesterone receptor (PgR), human EGF receptor 2 (Her2) and Ki-67 are important predictive and prognostic markers for making effective treatment decisions. Moreover, changes in these factors due to relapse are seen clinically, however, the frequency and clinical significance[for full text, please go to the a.m. URL], 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Published
2013
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50. Progrediente Fazialisparese durch einen benignen Parotistumor - ein Fallbericht

Author

Hasselbring, Laura, Grosheva, Maria, Ortmann, Monika, and Beutner, Dirk

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Ein benigner Tumor der Ohrspeicheldrüse geht in der Regel nicht mit einer peripheren Fazialisparese einher. Kasusitik: Wir berichten über einen Fall, bei dem im Rahmen einer entzündlich imponierenden Neubildung der Glandula Parotis eine komplette periphere Fazialisparese[for full text, please go to the a.m. URL], 81. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie

Published
2010

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