11 results on '"Hoff, Katja"'
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2. Functional loss of a noncanonical BCOR–PRC1.1 complex accelerates SHH-driven medulloblastoma formation
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Kutscher, Lena M., Okonechnikov, Konstantin, Batora, Nadja V., Clark, Jessica, Silva, Patricia B.G., Vouri, Mikaella, van Rijn, Sjoerd, Sieber, Laura, Statz, Britta, Gearhart, Micah D., Shiraishi, Ryo, Mack, Norman, Orr, Brent A., Korshunov, Andrey, Gudenas, Brian L., Smith, Kyle S., Mercier, Audrey L., Ayrault, Olivier, Hoshino, Mikio, Kool, Marcel, von Hoff, Katja, Graf, Norbert, Fleischhack, Gudrun, Bardwell, Vivian J., Pfister, Stefan M., Northcott, Paul A., and Kawauchi, Daisuke
- Abstract
In this study, Kutscher et al. investigated the transcriptional corepressor BCOR as a putative tumor suppressor and used a genetically engineered mouse model to delete exons 9/10 of Bcor in GNPs during development. Their data suggest that BCOR–PRC1.1 disruption leads to Igf2 overexpression, which transforms preneoplastic cells to malignant tumors.
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- 2020
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3. The molecular landscape of ETMR at diagnosis and relapse
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Lambo, Sander, Gröbner, Susanne N., Rausch, Tobias, Waszak, Sebastian M., Schmidt, Christin, Gorthi, Aparna, Romero, July Carolina, Mauermann, Monika, Brabetz, Sebastian, Krausert, Sonja, Buchhalter, Ivo, Koster, Jan, Zwijnenburg, Danny A., Sill, Martin, Hübner, Jens-Martin, Mack, Norman, Schwalm, Benjamin, Ryzhova, Marina, Hovestadt, Volker, Papillon-Cavanagh, Simon, Chan, Jennifer A., Landgraf, Pablo, Ho, Ben, Milde, Till, Witt, Olaf, Ecker, Jonas, Sahm, Felix, Sumerauer, David, Ellison, David W., Orr, Brent A., Darabi, Anna, Haberler, Christine, Figarella-Branger, Dominique, Wesseling, Pieter, Schittenhelm, Jens, Remke, Marc, Taylor, Michael D., Gil-da-Costa, Maria J., Łastowska, Maria, Grajkowska, Wiesława, Hasselblatt, Martin, Hauser, Peter, Pietsch, Torsten, Uro-Coste, Emmanuelle, Bourdeaut, Franck, Masliah-Planchon, Julien, Rigau, Valérie, Alexandrescu, Sanda, Wolf, Stephan, Li, Xiao-Nan, Schüller, Ulrich, Snuderl, Matija, Karajannis, Matthias A., Giangaspero, Felice, Jabado, Nada, von Deimling, Andreas, Jones, David T. W., Korbel, Jan O., von Hoff, Katja, Lichter, Peter, Huang, Annie, Bishop, Alexander J. R., Pfister, Stefan M., Korshunov, Andrey, and Kool, Marcel
- Abstract
Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2–4was not amplified frequently had germline mutations in DICER1or other microRNA-related aberrations such as somatic amplification of miR-17-92(also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.
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- 2019
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4. The landscape of genomic alterations across childhood cancers
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Gröbner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Hübschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jürgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Günther H., Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, Burkhardt, Birgit, Kratz, Christian P., Witt, Olaf, van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Frühwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Landgraf, Pablo, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Brors, Benedikt, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Schlesner, Matthias, Eils, Roland, Jones, David T. W., Lichter, Peter, Chavez, Lukas, Zapatka, Marc, and Pfister, Stefan M.
- Abstract
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
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- 2018
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5. DNA methylation-based classification of central nervous system tumours
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Capper, David, Jones, David T. W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, and Pfister, Stefan M.
- Abstract
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging—with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
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- 2018
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6. Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters.
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von Bueren, André O., Kortmann, Rolf-Dieter, von Hoff, Katja, Friedrich, Carsten, Mynarek, Martin, Müller, Klaus, Goschzik, Tobias, Mühlen, Anja zur, Gerber, Nicolas, Warmuth-Metz, Monika, Soerensen, Niels, Deinlein, Frank, Benesch, Martin, Zwiener, Isabella, Kwiecien, Robert, Faldum, Andreas, Bode, Udo, Fleischhack, Gudrun, Hovestadt, Volker, and Kool, Marcel
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- 2016
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7. A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors
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Neumann, Julia E, Wefers, Annika K, Lambo, Sander, Bianchi, Edoardo, Bockstaller, Marie, Dorostkar, Mario M, Meister, Valerie, Schindler, Pia, Korshunov, Andrey, von Hoff, Katja, Nowak, Johannes, Warmuth-Metz, Monika, Schneider, Marlon R, Renner-Müller, Ingrid, Merk, Daniel J, Shakarami, Mehdi, Sharma, Tanvi, Chavez, Lukas, Glass, Rainer, Chan, Jennifer A, Taketo, M Mark, Neumann, Philipp, Kool, Marcel, and Schüller, Ulrich
- Abstract
Embryonal tumors with multilayered rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with a fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh and Wnt signaling. Co-activation of these pathways in mouse neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts on the basis of histology and global gene-expression analyses, and that point to apical radial glia cells as the possible tumor cell of origin. Overexpression of LIN28A, which is a hallmark of human ETMRs, augments Sonic-hedgehog (Shh) and Wnt signaling in these precursor cells through the downregulation of let7-miRNA, and LIN28A/let7a interaction with the Shh pathway was detected at the level of Gli mRNA. Finally, human ETMR cells that were transplanted into immunocompromised host mice were responsive to the SHH inhibitor arsenic trioxide (ATO). Our work provides a novel mouse model in which to study this tumor type, demonstrates the driving role of Wnt and Shh activation in the growth of ETMRs and proposes downstream inhibition of Shh signaling as a therapeutic option for patients with ETMRs.
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- 2017
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8. Quality of survival and cognitive performance in children treated for medulloblastoma in the PNET 4 randomized controlled trial.
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Câmara-Costa, Hugo, Bull, Kim S, Kennedy, Colin, Wiener, Andreas, Calaminus, Gabriele, Resch, Anika, Kieffer, Virginie, Lalande, Clémence, Poggi, Geraldina, von Hoff, Katja, Grill, Jacques, Doz, François, Rutkowski, Stefan, Massimino, Maura, Kortmann, Rolf-Dieter, Lannering, Birgitta, Dellatolas, Georges, and Chevignard, Mathilde
- Abstract
The relationship between direct assessments of cognitive performance and questionnaires assessing quality of survival (QoS) is reported to be weak-to-nonexistent. Conversely, the associations between questionnaires evaluating distinct domains of QoS tend to be strong. This pattern remains understudied.
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- 2017
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9. Strategies to improve the quality of survival for childhood brain tumour survivors.
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Tallen, Gesche, Resch, Anika, Calaminus, Gabriele, Wiener, Andreas, Leiss, Ulrike, Pletschko, Thomas, Friedrich, Carsten, Langer, Thorsten, Grabow, Desiree, Driever, Pablo Hernáiz, Kortmann, Rolf-Dieter, Timmermann, Beate, Pietsch, Torsten, Warmuth-Metz, Monika, Bison, Brigitte, Thomale, Ulrich-Wilhelm, Krauss, Jürgen, Mynarek, Martin, von Hoff, Katja, and Ottensmeier, Holger
- Abstract
Background Tumours of the central nervous system (CNS) are the most frequent solid tumours and the second most frequent type of cancer in children and adolescents. Overall survival has continuously improved in Germany, since an increasing number of patients have been treated according to standardised, multicentre, multimodal treatment recommendations, trials of the German Paediatric Brain Tumour Consortium (HIT-Network) or the International Society of Paediatric Oncology-Europe (SIOP-E) during the last decades. Today, two out of three patients survive. At least 8000 long-term childhood brain tumour survivors (CBTS) are currently living in Germany. They face lifelong disease- and treatment-related late effects (LE) and associated socioeconomic problems more than many other childhood cancer survivors (CCS). Method We review the LE and resulting special needs of this particular group of CCS. Results Despite their increasing relevance for future treatment optimisation, neither the diversity of chronic and cumulative LE nor their pertinent risk factors and subsequent impact on quality of survival have yet been comprehensively addressed for CBTS treated according to HIT- or SIOP-E-protocols. Evidence-based information to empower survivors and stakeholders, as well as medical expertise to manage their individual health care, psychosocial and educational/vocational needs must still be generated and established. Conclusion The establishment of a long-term research- and care network in Germany shall contribute to a European platform, that aims at optimising CBTSs' transition into adulthood as resilient individuals with high quality of survival including optimal levels of activity, participation and acceptance by society. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Neuropsychological short assessment of disease- and treatment-related intelligence deficits in children with brain tumours.
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Ottensmeier, Holger, Zimolong, Bernhard, Wolff, Johannes E., Ehrich, Jochen, Galley, Niels, von Hoff, Katja, Kuehl, Joachim, and Rutkowski, Stefan
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Objective The Wuerzburger Psychologische Kurz-Diagnostik (WUEP-KD) is a short screening battery for cognitive deficits in children with brain tumour. We report on its psychometric quality and testing efficiency. Material and methods WUEP-KD was founded on Cattell-Horn-Carroll (CHC) framework of cognitive abilities. We assessed the construct validity of the short battery by conducting factor analysis and the concurrent validity by multiple linear regressions with Kaufman Assessment Battery for Children (K-ABC). The concurrent validity was explored by multiple linear regressions with Wechsler Intelligence Scale for Children (WISC). The discriminant validity was examined by a reanalysis of harmful effects of brain tumour treatments in a medulloblastoma cohort. Results The construct validity assessment revealed three neuropsychological domains: cognitive operations, executive abilities, and psychomotor abilities. The retest reliabilities for individual testing and the convergent coefficients of the WUEP-KD with K-ABC and WISC yielded satisfactory results. The cognitive effects of different treatment modalities in the medulloblastoma cohort matched exactly previously reported data on the decline of general intelligence scores and delivered the details for the harmful effects. An in-depth analysis based on Hedges' g effect sizes confirmed specific harmful late effects on all abilities of cognitive operations, on the executive ability of perceptual speed and on psychomotor ability of movement steadiness. Conclusion WUEP-KD is a valid and efficient short test instrument, which may be especially useful in larger cohorts, multicenter settings or if patients do not tolerate longer tests. Due to its foundation on the CHC framework, our findings provide a rationale to create a common data set along with scores from other factor-based tests in international studies. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Author Correction: The landscape of genomic alterations across childhood cancers
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Gröbner, Susanne, Worst, Barbara, Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa, Johann, Pascal, Balasubramanian, Gnana, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Hübschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jürgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas, Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Günther, Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan, Vassal, Gilles, Witt, Hendrik, Burkhardt, Birgit, Kratz, Christian, Witt, Olaf, Tilburg, Cornelis, Kramm, Christof, Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Frühwald, Michael, Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Landgraf, Pablo, Koster, Jan, Resnick, Adam, Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela, Zwijnenburg, Danny, Raman, Pichai, Brors, Benedikt, Weber, Ursula, Northcott, Paul, Pajtler, Kristian, Kool, Marcel, Piro, Rosario, Korbel, Jan, Schlesner, Matthias, Eils, Roland, Jones, David, Lichter, Peter, Chavez, Lukas, Zapatka, Marc, and Pfister, Stefan
- Abstract
In this Article, author Benedikt Brors was erroneously associated with affiliation number ‘8’ (Department of Developmental Neurobiology, St Jude Children’s Research Hospital, Memphis, Tennessee, USA); the author’s two other affiliations (affiliations ‘3’ and ‘7’, both at the German Cancer Research Center (DKFZ)) were correct. This has been corrected online.
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- 2018
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