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2. Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K, Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G, Hayden, James T, Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte EG, Tops, Bastiaan BJ, Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M, Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J, Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M, Sahm, Felix, Solomon, David A, and Jones, David TW

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Pediatric, Genetics, Rare Diseases, Pediatric Cancer, Cancer, Pediatric Research Initiative, Neurosciences, Brain Cancer, Brain Disorders, Child, Child, Preschool, Female, Humans, Infant, Male, Cell Cycle Proteins, Central Nervous System Neoplasms, DNA Methylation, DNA-Binding Proteins, Neuroectodermal Tumors, Primitive, RNA-Binding Proteins, Transcription Factors, Tumor Suppressor Proteins, Wnt Signaling Pathway, PLAGL1, PLAGL2, Molecular neuro-oncology, Pediatric cancer, Clinical Sciences, Neurology & Neurosurgery
Abstract

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

Published
2023

5. Pediatric pineoblastoma: A pooled outcome study of North American and Australian therapeutic data

Author

Hansford, Jordan R, Huang, Jie, Endersby, Raelene, Dodgshun, Andrew J, Li, Bryan K, Hwang, Eugene, Leary, Sarah, Gajjar, Amar, Von Hoff, Katja, Wells, Olivia, Wray, Alison, Kotecha, Rishi S, Raleigh, David R, Stoller, Schuyler, Mueller, Sabine, Schild, Steven E, Bandopadhayay, Pratiti, Fouladi, Maryam, Bouffet, Eric, Huang, Annie, Onar-Thomas, Arzu, and Gottardo, Nicholas G

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cancer, Clinical Research, Pediatric, Clinical Trials and Supportive Activities, Good Health and Well Being, pediatrics, pineoblastoma, retrospective study
Abstract

BackgroundPineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years. These included only occasional children with pineoblastoma, making clinical features difficult to interpret and determinants of outcome difficult to ascertain.Patients and methodsCentrally or independently reviewed series with treatment and survival data from North American and Australian cases were pooled. To investigate associations between variables, Fisher's exact tests, Wilcoxon-Mann-Whitney tests, and Spearman correlations were used. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analyses.ResultsWe describe a pooled cohort of 178 pineoblastoma cases from Children's Oncology Group (n = 82) and institutional series (n = 96) over 30 years. Children

Published
2022

6. Correction to: Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K., Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G., Hayden, James T., Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte E. G., Tops, Bastiaan B. J., Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M., Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J., Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M., Sahm, Felix, Solomon, David A., and Jones, David T. W.

Published
2023
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7. Identification of low and very high-risk patients with non-WNT/non-SHH medulloblastoma by improved clinico-molecular stratification of the HIT2000 and I-HIT-MED cohorts

Author

Mynarek, Martin, Obrecht, Denise, Sill, Martin, Sturm, Dominik, Kloth-Stachnau, Katja, Selt, Florian, Ecker, Jonas, von Hoff, Katja, Juhnke, Björn-Ole, Goschzik, Tobias, Pietsch, Torsten, Bockmayr, Michael, Kool, Marcel, von Deimling, Andreas, Witt, Olaf, Schüller, Ulrich, Benesch, Martin, Gerber, Nicolas U., Sahm, Felix, Jones, David T. W., Korshunov, Andrey, Pfister, Stefan M., Rutkowski, Stefan, and Milde, Till

Published
2023
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9. Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa—Results of the HIT 2000 trial.

Author

Mynarek, Martin, Rossius, Anne, Guiard, Anika, Ottensmeier, Holger, Hoff, Katja von, Obrecht-Sturm, Denise, Bußenius, Lisa, Friedrich, Carsten, Bueren, Andre O von, Gerber, Nicolas U, Traunwieser, Thomas, Kortmann, Rolf-Dieter, Warmuth-Metz, Monika, Bison, Brigitte, Thomale, Ulrich-W, Krauss, Juergen, Pietsch, Torsten, Clifford, Steven C, Pfister, Stefan M, and Sturm, Dominik

Published
2024
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10. Clinical and molecular characterization of isolated M1 disease in pediatric medulloblastoma: experience from the German HIT-MED studies

Author

Obrecht, Denise, Mynarek, Martin, Hagel, Christian, Kwiecien, Robert, Spohn, Michael, Bockmayr, Michael, Bison, Brigitte, Pfister, Stefan M., Jones, David T. W., Sturm, Dominik, von Deimling, Andreas, Sahm, Felix, von Hoff, Katja, Juhnke, B.-Ole, Benesch, Martin, Gerber, Nicolas U., Friedrich, Carsten, von Bueren, André O., Kortmann, Rolf-Dieter, Schwarz, Rudolf, Pietsch, Torsten, Fleischhack, Gudrun, Schüller, Ulrich, and Rutkowski, Stefan

Published
2022
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11. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

Author

Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, and Pfister, Stefan M

Subjects
Humans, Medulloblastoma, Cerebellar Neoplasms, Genetic Predisposition to Disease, Risk Factors, Retrospective Studies, Prospective Studies, Reproducibility of Results, Predictive Value of Tests, Gene Expression Profiling, Pedigree, DNA Mutational Analysis, DNA Methylation, Heredity, Phenotype, Germ-Line Mutation, Models, Genetic, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Young Adult, Genetic Testing, Transcriptome, Biomarkers, Tumor, Progression-Free Survival, Exome Sequencing, Brain Cancer, Genetics, Cancer, Human Genome, Pediatric, Pediatric Cancer, Rare Diseases, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes.InterpretationGenetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics.FundingGerman Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

Published
2018

12. DNA methylation-based classification of central nervous system tumours.

Author

Capper, David, Jones, David TW, 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, and Jones, Chris

Subjects
Humans, Central Nervous System Neoplasms, Cohort Studies, Reproducibility of Results, DNA Methylation, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Young Adult, Unsupervised Machine Learning, and over, Preschool, General Science & Technology
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.

Published
2018

13. PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum

Author

Alhalabi, Karam T., Stichel, Damian, Sievers, Philipp, Peterziel, Heike, Sommerkamp, Alexander C., Sturm, Dominik, Wittmann, Andrea, Sill, Martin, Jäger, Natalie, Beck, Pengbo, Pajtler, Kristian W., Snuderl, Matija, Jour, George, Delorenzo, Michael, Martin, Allison M., Levy, Adam, Dalvi, Nagma, Hansford, Jordan R., Gottardo, Nicholas G., Uro-Coste, Emmanuelle, Maurage, Claude-Alain, Godfraind, Catherine, Vandenbos, Fanny, Pietsch, Torsten, Kramm, Christof, Filippidou, Maria, Kattamis, Antonis, Jones, Chris, Øra, Ingrid, Mikkelsen, Torben Stamm, Zapotocky, Michal, Sumerauer, David, Scheie, David, McCabe, Martin, Wesseling, Pieter, Tops, Bastiaan B. J., Kranendonk, Mariëtte E. G., Karajannis, Matthias A., Bouvier, Nancy, Papaemmanuil, Elli, Dohmen, Hildegard, Acker, Till, von Hoff, Katja, Schmid, Simone, Miele, Evelina, Filipski, Katharina, Kitanovski, Lidija, Krskova, Lenka, Gojo, Johannes, Haberler, Christine, Alvaro, Frank, Ecker, Jonas, Selt, Florian, Milde, Till, Witt, Olaf, Oehme, Ina, Kool, Marcel, von Deimling, Andreas, Korshunov, Andrey, Pfister, Stefan M., Sahm, Felix, and Jones, David T. W.

Published
2021
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14. Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study

Author

Liu, Anthony P. Y., Li, Bryan K., Pfaff, Elke, Gudenas, Brian, Vasiljevic, Alexandre, Orr, Brent A., Dufour, Christelle, Snuderl, Matija, Karajannis, Matthias A., Rosenblum, Marc K., Hwang, Eugene I., Ng, Ho-Keung, Hansford, Jordan R., Szathmari, Alexandru, Faure-Conter, Cécile, Merchant, Thomas E., Levine, Max, Bouvier, Nancy, von Hoff, Katja, Mynarek, Martin, Rutkowski, Stefan, Sahm, Felix, Kool, Marcel, Hawkins, Cynthia, Onar-Thomas, Arzu, Robinson, Giles W., Gajjar, Amar, Pfister, Stefan M., Bouffet, Eric, Northcott, Paul A., Jones, David T. W., and Huang, Annie

Published
2021
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15. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

Author

Ramaswamy, Vijay, Hielscher, Thomas, Mack, Stephen C, Lassaletta, Alvaro, Lin, Tong, Pajtler, Kristian W, Jones, David TW, Luu, Betty, Cavalli, Florence MG, Aldape, Kenneth, Remke, Marc, Mynarek, Martin, Rutkowski, Stefan, Gururangan, Sridharan, McLendon, Roger E, Lipp, Eric S, Dunham, Christopher, Hukin, Juliette, Eisenstat, David D, Fulton, Dorcas, van Landeghem, Frank KH, Santi, Mariarita, van Veelen, Marie-Lise C, Van Meir, Erwin G, Osuka, Satoru, Fan, Xing, Muraszko, Karin M, Tirapelli, Daniela PC, Oba-Shinjo, Sueli M, Marie, Suely KN, Carlotti, Carlos G, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Faria, Claudia C, Nunes, Sofia, Mora, Jaume, Hamilton, Ronald L, Hauser, Peter, Jabado, Nada, Petrecca, Kevin, Jung, Shin, Massimi, Luca, Zollo, Massimo, Cinalli, Giuseppe, Bognár, László, Klekner, Almos, Hortobágyi, Tibor, Leary, Sarah, Ermoian, Ralph P, Olson, James M, Leonard, Jeffrey R, Gardner, Corrine, Grajkowska, Wieslawa A, Chambless, Lola B, Cain, Jason, Eberhart, Charles G, Ahsan, Sama, Massimino, Maura, Giangaspero, Felice, Buttarelli, Francesca R, Packer, Roger J, Emery, Lyndsey, Yong, William H, Soto, Horacio, Liau, Linda M, Everson, Richard, Grossbach, Andrew, Shalaby, Tarek, Grotzer, Michael, Karajannis, Matthias A, Zagzag, David, Wheeler, Helen, von Hoff, Katja, Alonso, Marta M, Tuñon, Teresa, Schüller, Ulrich, Zitterbart, Karel, Sterba, Jaroslav, Chan, Jennifer A, Guzman, Miguel, Elbabaa, Samer K, Colman, Howard, Dhall, Girish, Fisher, Paul G, Fouladi, Maryam, Gajjar, Amar, Goldman, Stewart, Hwang, Eugene, Kool, Marcel, Ladha, Harshad, Vera-Bolanos, Elizabeth, Wani, Khalida, Lieberman, Frank, Mikkelsen, Tom, Omuro, Antonio M, Pollack, Ian F, Prados, Michael, Robins, H Ian, and Soffietti, Riccardo

Subjects
Humans, Ependymoma, Infratentorial Neoplasms, Combined Modality Therapy, Retrospective Studies, Cohort Studies, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Cytoreduction Surgical Procedures, Rare Diseases, Pediatric Cancer, Cancer, Pediatric, Patient Safety, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePosterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.ResultsMolecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation.ConclusionThe most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Published
2016

16. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

Author

Sturm, Dominik, Orr, Brent A, Toprak, Umut H, Hovestadt, Volker, Jones, David TW, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A, Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J, Balasubramanian, Gnanaprakash, Worst, Barbara C, Pajtler, Kristian W, Brabetz, Sebastian, Johann, Pascal D, Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M, Remke, Marc, Phillips, Joanna J, Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C, Schniederjan, Matthew J, Santi, Mariarita, Buccoliero, Anna M, Dahiya, Sonika, Kramm, Christof M, von Bueren, André O, von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C, Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U, Shalaby, Tarek, Grotzer, Michael, van Meter, Timothy, Monoranu, Camelia-Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S, Taylor, Michael D, and Jones, Chris

Subjects
Humans, Neuroectodermal Tumors, Central Nervous System Neoplasms, Trans-Activators, Proto-Oncogene Proteins, Tumor Suppressor Proteins, Repressor Proteins, Gene Expression Profiling, Signal Transduction, DNA Methylation, Gene Expression Regulation, Neoplastic, Amino Acid Sequence, Molecular Sequence Data, Child, Forkhead Transcription Factors, Neuroblastoma, Cancer, Pediatric, Neurosciences, Brain Disorders, Rare Diseases, Orphan Drug, Brain Cancer, Pediatric Research Initiative, Pediatric Cancer, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Published
2016

18. Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations

Author

Pfaff, Elke, Aichmüller, Christian, Sill, Martin, Stichel, Damian, Snuderl, Matija, Karajannis, Matthias A., Schuhmann, Martin U., Schittenhelm, Jens, Hasselblatt, Martin, Thomas, Christian, Korshunov, Andrey, Rhizova, Marina, Wittmann, Andrea, Kaufhold, Anna, Iskar, Murat, Ketteler, Petra, Lohmann, Dietmar, Orr, Brent A., Ellison, David W., von Hoff, Katja, Mynarek, Martin, Rutkowski, Stefan, Sahm, Felix, von Deimling, Andreas, Lichter, Peter, Kool, Marcel, Zapatka, Marc, Pfister, Stefan M., and Jones, David T. W.

Published
2020
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19. Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups

Author

Pajtler, Kristian W, Witt, Hendrik, Sill, Martin, Jones, David TW, Hovestadt, Volker, Kratochwil, Fabian, Wani, Khalida, Tatevossian, Ruth, Punchihewa, Chandanamali, Johann, Pascal, Reimand, Jüri, Warnatz, Hans-Jörg, Ryzhova, Marina, Mack, Steve, Ramaswamy, Vijay, Capper, David, Schweizer, Leonille, Sieber, Laura, Wittmann, Andrea, Huang, Zhiqin, van Sluis, Peter, Volckmann, Richard, Koster, Jan, Versteeg, Rogier, Fults, Daniel, Toledano, Helen, Avigad, Smadar, Hoffman, Lindsey M, Donson, Andrew M, Foreman, Nicholas, Hewer, Ekkehard, Zitterbart, Karel, Gilbert, Mark, Armstrong, Terri S, Gupta, Nalin, Allen, Jeffrey C, Karajannis, Matthias A, Zagzag, David, Hasselblatt, Martin, Kulozik, Andreas E, Witt, Olaf, Collins, V Peter, von Hoff, Katja, Rutkowski, Stefan, Pietsch, Torsten, Bader, Gary, Yaspo, Marie-Laure, von Deimling, Andreas, Lichter, Peter, Taylor, Michael D, Gilbertson, Richard, Ellison, David W, Aldape, Kenneth, Korshunov, Andrey, Kool, Marcel, and Pfister, Stefan M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Cancer, Adaptor Proteins, Signal Transducing, Adolescent, Adult, Age Factors, Aged, Central Nervous System Neoplasms, Child, Child, Preschool, DNA Methylation, Ependymoma, Female, Gene Dosage, Gene Expression Profiling, Gene Fusion, Humans, Infant, Male, Middle Aged, Phosphoproteins, Transcription Factors, Transcription, Genetic, YAP-Signaling Proteins, Young Adult, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

Published
2015

20. CDKN2A deletion in supratentorial ependymoma with RELA alteration indicates a dismal prognosis: a retrospective analysis of the HIT ependymoma trial cohort

Author

Jünger, Stephanie T., Andreiuolo, Felipe, Mynarek, Martin, Wohlers, Inken, Rahmann, Sven, Klein-Hitpass, Ludger, Dörner, Evelyn, zur Mühlen, Anja, Velez-Char, Natalia, von Hoff, Katja, Warmuth-Metz, Monika, Kortmann, Rolf-Dieter, Timmermann, Beate, von Bueren, Andre, Rutkowski, Stefan, and Pietsch, Torsten

Published
2020
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21. The molecular landscape of ETMR at diagnosis and relapse

Author

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

Published
2019
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22. Clinical outcome of pediatric medulloblastoma patients with Li–Fraumeni syndrome

Author

Kolodziejczak, Anna S, primary, Guerrini-Rousseau, Lea, additional, Planchon, Julien Masliah, additional, Ecker, Jonas, additional, Selt, Florian, additional, Mynarek, Martin, additional, Obrecht, Denise, additional, Sill, Martin, additional, Autry, Robert J, additional, Stutheit-Zhao, Eric, additional, Hirsch, Steffen, additional, Amouyal, Elsa, additional, Dufour, Christelle, additional, Ayrault, Olivier, additional, Torrejon, Jacob, additional, Waszak, Sebastian M, additional, Ramaswamy, Vijay, additional, Pentikainen, Virve, additional, Demir, Haci Ahmet, additional, Clifford, Steven C, additional, Schwalbe, Ed C, additional, Massimi, Luca, additional, Snuderl, Matija, additional, Galbraith, Kristyn, additional, Karajannis, Matthias A, additional, Hill, Katherine, additional, Li, Bryan K, additional, Walsh, Mike, additional, White, Christine L, additional, Redmond, Shelagh, additional, Loizos, Loizou, additional, Jakob, Marcus, additional, Kordes, Uwe R, additional, Schmid, Irene, additional, Hauer, Julia, additional, Blattmann, Claudia, additional, Filippidou, Maria, additional, Piccolo, Gianluca, additional, Scheurlen, Wolfram, additional, Farrag, Ahmed, additional, Grund, Kerstin, additional, Sutter, Christian, additional, Pietsch, Torsten, additional, Frank, Stephan, additional, Schewe, Denis M, additional, Malkin, David, additional, Ben-Arush, Myriam, additional, Sehested, Astrid, additional, Wong, Tai-Tong, additional, Wu, Kuo-Sheng, additional, Liu, Yen-Lin, additional, Carceller, Fernando, additional, Mueller, Sabine, additional, Stoller, Schuyler, additional, Taylor, Michael D, additional, Tabori, Uri, additional, Bouffet, Eric, additional, Kool, Marcel, additional, Sahm, Felix, additional, von Deimling, Andreas, additional, Korshunov, Andrey, additional, von Hoff, Katja, additional, Kratz, Christian P, additional, Sturm, Dominik, additional, Jones, David T W, additional, Rutkowski, Stefan, additional, van Tilburg, Cornelis M, additional, Witt, Olaf, additional, Bougeard, Gaëlle, additional, Pajtler, Kristian W, additional, Pfister, Stefan M, additional, Bourdeaut, Franck, additional, and Milde, Till, additional

Published
2023
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23. A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial ZFTA-fused ependymoma

Author

Ng, Chia Huan, primary, Obrecht, Denise, additional, Wells, Olivia, additional, Zapotocky, Michal, additional, Sumerauer, David, additional, Coltin, Hallie, additional, Khuong-Quang, Dong-Anh, additional, Eisenstat, David D, additional, Kinross, Kathryn M, additional, White, Christine L, additional, Algar, Elizabeth M, additional, Luck, Amanda, additional, Witt, Hendrik, additional, Schüller, Ulrich, additional, Mynarek, Martin, additional, Pietsch, Torsten, additional, Gerber, Nicolas U, additional, Benesch, Martin, additional, Warmuth-Metz, Monika, additional, Kortmann, Rolf, additional, Bison, Brigitte, additional, Taylor, Michael D, additional, Rutkowski, Stefan, additional, Pfister, Stefan M, additional, Jones, David T W, additional, Gottardo, Nicholas G, additional, von Hoff, Katja, additional, Pajtler, Kristian W, additional, Ramaswamy, Vijay, additional, and Hansford, Jordan R, additional

Published
2023
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24. Focal versus craniospinal radiation for disseminated atypical teratoid/rhabdoid tumor following favorable response to systemic therapy

Author

Aridgides, Paul D., primary, Mahajan, Anita, additional, Eaton, Bree, additional, Wang, Dongliang, additional, Timmerman, Beate, additional, Früwald, Michael C., additional, Nemes, Karolina, additional, Deck, Jared, additional, Yamasaki, Kai, additional, Von Hoff, Katja, additional, Lafay‐Cousin, Lucie, additional, Reddy, Alyssa, additional, and Lo, Andrea C., additional

Published
2023
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25. A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial ZFTA-fused ependymoma

Author

Ng, Chia Huan, Obrecht, Denise, Wells, Olivia, Zapotocky, Michal, Sumerauer, David, Coltin, Hallie, Khuong-Quang, Dong-Anh, Eisenstat, David D; https://orcid.org/0000-0002-5976-0798, Kinross, Kathryn M, White, Christine L, Algar, Elizabeth M, Luck, Amanda, Witt, Hendrik, Schüller, Ulrich; https://orcid.org/0000-0002-8731-1121, Mynarek, Martin; https://orcid.org/0000-0003-3302-2719, Pietsch, Torsten, Gerber, Nicolas U, Benesch, Martin, Warmuth-Metz, Monika; https://orcid.org/0000-0002-3544-319X, Kortmann, Rolf, Bison, Brigitte, Taylor, Michael D, Rutkowski, Stefan, Pfister, Stefan M, Jones, David T W; https://orcid.org/0000-0002-2036-5141, Gottardo, Nicholas G; https://orcid.org/0000-0002-1082-6776, von Hoff, Katja; https://orcid.org/0000-0002-5669-8546, Pajtler, Kristian W; https://orcid.org/0000-0002-3562-6121, Ramaswamy, Vijay; https://orcid.org/0000-0002-6557-895X, Hansford, Jordan R; https://orcid.org/0000-0001-7733-383X, Ng, Chia Huan, Obrecht, Denise, Wells, Olivia, Zapotocky, Michal, Sumerauer, David, Coltin, Hallie, Khuong-Quang, Dong-Anh, Eisenstat, David D; https://orcid.org/0000-0002-5976-0798, Kinross, Kathryn M, White, Christine L, Algar, Elizabeth M, Luck, Amanda, Witt, Hendrik, Schüller, Ulrich; https://orcid.org/0000-0002-8731-1121, Mynarek, Martin; https://orcid.org/0000-0003-3302-2719, Pietsch, Torsten, Gerber, Nicolas U, Benesch, Martin, Warmuth-Metz, Monika; https://orcid.org/0000-0002-3544-319X, Kortmann, Rolf, Bison, Brigitte, Taylor, Michael D, Rutkowski, Stefan, Pfister, Stefan M, Jones, David T W; https://orcid.org/0000-0002-2036-5141, Gottardo, Nicholas G; https://orcid.org/0000-0002-1082-6776, von Hoff, Katja; https://orcid.org/0000-0002-5669-8546, Pajtler, Kristian W; https://orcid.org/0000-0002-3562-6121, Ramaswamy, Vijay; https://orcid.org/0000-0002-6557-895X, and Hansford, Jordan R; https://orcid.org/0000-0001-7733-383X

Abstract

BACKGROUND ZFTA-RELA (formerly known as c11orf-RELA) fused supratentorial ependymoma (ZFTAfus ST-EPN) has been recognized as a novel entity in the 2016 WHO classification of CNS tumors and further defined in the recent 2021 edition. ZFTAfus ST-EPN was reported to portend poorer prognosis when compared to its counterpart, YAP1 ST-EPN in some previously published series. The aim of this study was to determine the treatment outcome of molecularly confirmed and conventionally treated ZFTAfus ST-EPN patients treated in multiple institutions. METHODS We conducted a retrospective analysis of all pediatric patients with molecularly confirmed ZFTAfus ST-EPN patients treated in multiple institutions in 5 different countries (Australia, Canada, Germany, Switzerland, and Czechia). Survival outcomes were analyzed and correlated with clinical characteristics and treatment approaches. RESULTS A total of 108 patients were collated from multiple institutions in 5 different countries across three continents. We found across the entire cohort that the 5- and 10-year PFS were 65% and 63%, respectively. The 5- and 10-year OS of this cohort of patients were 87% and 73%. The rates of gross total resection (GTR) were high with 84 out of 108 (77.8%) patients achieving GTR. The vast majority of patients also received post-operative radiotherapy, 98 out of 108 (90.7%). Chemotherapy did not appear to provide any survival benefit in our patient cohort. CONCLUSION This is the largest study to date of contemporaneously treated molecularly confirmed ZFTAfus ST-EPN patients which identified markedly improved survival outcomes compared to previously published series. This study also re-emphasizes the importance of maximal surgical resection in achieving optimal outcomes in pediatric patients with supratentorial ependymoma.

Published
2023

26. Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features – a retrospective analysis of the HIT ependymoma trial cohort

Author

Jünger, Stephanie T., Mynarek, Martin, Wohlers, Inken, Dörner, Evelyn, Mühlen, Anja zur, Velez-Char, Natalia, von Hoff, Katja, Rutkowski, Stefan, Warmuth-Metz, Monika, Kortmann, Rolf-Dieter, Timmermann, Beate, Rahmann, Sven, Klein-Hitpass, Ludger, von Bueren, Andre O., and Pietsch, Torsten

Published
2019
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27. Risk prediction in early childhood sonic hedgehog medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than 2 subgroups

Author

Tonn, Svenja, primary, Korshunov, Andrey, additional, Obrecht, Denise, additional, Sill, Martin, additional, Spohn, Michael, additional, von Hoff, Katja, additional, Milde, Till, additional, Pietsch, Torsten, additional, Goschzik, Tobias, additional, Bison, Brigitte, additional, Juhnke, Björn-Ole, additional, Struve, Nina, additional, Sturm, Dominik, additional, Sahm, Felix, additional, Bockmayr, Michael, additional, Friedrich, Carsten, additional, von Bueren, André O, additional, Gerber, Nicolas U, additional, Benesch, Martin, additional, Jones, David T W, additional, Kool, Marcel, additional, Wefers, Annika K, additional, Schüller, Ulrich, additional, Pfister, Stefan M, additional, Rutkowski, Stefan, additional, and Mynarek, Martin, additional

Published
2023
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28. A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors

Author

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

Subjects
Embryonal tumors -- Diagnosis -- Care and treatment -- Genetic aspects, Sonic hedgehog -- Health aspects, Cellular signal transduction -- Genetic aspects -- Health aspects, Gene expression -- Health aspects, Biological sciences, Health
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., Author(s): Julia E Neumann [1, 2, 3]; Annika K Wefers [1, 4, 5, 6]; Sander Lambo [7]; Edoardo Bianchi [1]; Marie Bockstaller [1]; Mario M Dorostkar [1, 8]; Valerie Meister [...]

Published
2017
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29. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Author

Pajtler, Kristian W., Mack, Stephen C., Ramaswamy, Vijay, Smith, Christian A., Witt, Hendrik, Smith, Amy, Hansford, Jordan R., von Hoff, Katja, Wright, Karen D., Hwang, Eugene, Frappaz, Didier, Kanemura, Yonehiro, Massimino, Maura, Faure-Conter, Cécile, Modena, Piergiorgio, Tabori, Uri, Warren, Katherine E., Holland, Eric C., Ichimura, Koichi, Giangaspero, Felice, Castel, David, von Deimling, Andreas, Kool, Marcel, Dirks, Peter B., Grundy, Richard G., Foreman, Nicholas K., Gajjar, Amar, Korshunov, Andrey, Finlay, Jonathan, Gilbertson, Richard J., Ellison, David W., Aldape, Kenneth D., Merchant, Thomas E., Bouffet, Eric, Pfister, Stefan M., and Taylor, Michael D.

Published
2017
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30. Identification of low and very high-risk patients with non-WNT/non-SHH medulloblastoma by improved clinico-molecular stratification of the HIT2000 and I-HIT-MED cohorts

Author

Mynarek, Martin, primary, Obrecht, Denise, additional, Sill, Martin, additional, Sturm, Dominik, additional, Kloth-Stachnau, Katja, additional, Selt, Florian, additional, Ecker, Jonas, additional, von Hoff, Katja, additional, Juhnke, Björn-Ole, additional, Goschzik, Tobias, additional, Pietsch, Torsten, additional, Bockmayr, Michael, additional, Kool, Marcel, additional, von Deimling, Andreas, additional, Witt, Olaf, additional, Schüller, Ulrich, additional, Benesch, Martin, additional, Gerber, Nicolas U., additional, Sahm, Felix, additional, Jones, David T. W., additional, Korshunov, Andrey, additional, Pfister, Stefan M., additional, Rutkowski, Stefan, additional, and Milde, Till, additional

Published
2022
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31. Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, primary, Sill, Martin, additional, Wittmann, Andrea, additional, Joshi, Piyush, additional, Stichel, Damian, additional, Beck, Pengbo, additional, Okonechnikow, Konstantin, additional, Sievers, Philipp, additional, Wefers, Annika K., additional, Roncaroli, Federico, additional, Avula, Shivaram, additional, McCabe, Martin G., additional, Hayden, James T., additional, Wesseling, Pieter, additional, Øra, Ingrid, additional, Nistér, Monica, additional, Kranendonk, Mariëtte E. G., additional, Tops, Bastiaan B. J., additional, Zapotocky, Michal, additional, Zamecnik, Josef, additional, Vasiljevic, Alexandre, additional, Fenouil, Tanguy, additional, Meyronet, David, additional, von Hoff, Katja, additional, Schüller, Ulrich, additional, Loiseau, Hugues, additional, Figarella-Branger, Dominique, additional, Kramm, Christof M., additional, Sturm, Dominik, additional, Scheie, David, additional, Rauramaa, Tuomas, additional, Pesola, Jouni, additional, Gojo, Johannes, additional, Haberler, Christine, additional, Brandner, Sebastian, additional, Jacques, Tom, additional, Sexton Oates, Alexandra, additional, Saffery, Richard, additional, Koscielniak, Ewa, additional, Baker, Suzanne J., additional, Yip, Stephen, additional, Snuderl, Matija, additional, Ud Din, Nasir, additional, Samuel, David, additional, Schramm, Kathrin, additional, Blattner-Johnson, Mirjam, additional, Selt, Florian, additional, Ecker, Jonas, additional, Milde, Till, additional, von Deimling, Andreas, additional, Korshunov, Andrey, additional, Perry, Arie, additional, Pfister, Stefan M., additional, Sahm, Felix, additional, Solomon, David A., additional, and Jones, David T. W., additional

Published
2022
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32. Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

Author

Gerber, Nicolas U., von Hoff, Katja, Resch, Anika, Ottensmeier, Holger, Kwiecien, Robert, Faldum, Andreas, Matuschek, Christiane, Hornung, Dagmar, Bremer, Michael, Benesch, Martin, Pietsch, Torsten, Warmuth-Metz, Monika, Kuehl, Joachim, Rutkowski, Stefan, and Kortmann, Rolf D.

Published
2014
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33. Postponed Is Not Canceled: Role of Craniospinal Radiation Therapy in the Management of Recurrent Infant Medulloblastoma—An Experience From the HIT-REZ 1997 & 2005 Studies

Author

Müller, Klaus, Mynarek, Martin, Zwiener, Isabella, Siegler, Nele, Zimmermann, Martina, Christiansen, Hans, Budach, Wilfried, Henke, Guido, Warmuth-Metz, Monika, Pietsch, Torsten, von Hoff, Katja, von Bueren, Andre, Bode, Udo, Rutkowski, Stefan, Kortmann, Rolf-Dieter, Fleischhack, Gudrun, and Tippelt, Stephan

Published
2014
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35. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus

Author

Ramaswamy, Vijay, Remke, Marc, Bouffet, Eric, Bailey, Simon, Clifford, Steven C., Doz, Francois, Kool, Marcel, Dufour, Christelle, Vassal, Gilles, Milde, Till, Witt, Olaf, von Hoff, Katja, Pietsch, Torsten, Northcott, Paul A., Gajjar, Amar, Robinson, Giles W., Padovani, Laetitia, André, Nicolas, Massimino, Maura, Pizer, Barry, Packer, Roger, Rutkowski, Stefan, Pfister, Stefan M., Taylor, Michael D., and Pomeroy, Scott L.

Published
2016
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36. Evidence of neural crest cell origin of a DICER1 mutant CNS sarcoma in a child with DICER1 syndrome and NRAS‐mutant neurocutaneous melanosis

Author

Schweizer, Leonille, primary, Hartmann, Wolfgang, additional, Koch, Arend, additional, Nunninger, Maximilian, additional, Thomale, Ulrich‐Wilhelm, additional, Pennacchietti, Valentina, additional, Tietze, Anna, additional, Horn, Denise, additional, Pajtler, Kristian W., additional, Hirsch, Steffen, additional, Wieland, Ilse, additional, Deubzer, Hedwig, additional, Rossi, Rainer, additional, Driever, Pablo Hernáiz, additional, von Hoff, Katja, additional, and von Zezschwitz, Barbara, additional

Published
2022
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37. Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study

Author

von Hoff, Katja, Haberler, Christine, Schmitt-Hoffner, Felix, Schepke, Elizabeth, de Rojas, Teresa, Jacobs, Sandra, Zapotocky, Michal, Sumerauer, David, Perek-Polnik, Marta, Dufour, Christelle, van Vuurden, Dannis, Slavc, Irene, Gojo, Johannes, Pickles, Jessica C, Gerber, Nicolas U, Massimino, Maura, Gil-da-Costa, Maria Joao, Garami, Miklos, Kumirova, Ella, Sehested, Astrid, Scheie, David, Cruz, Ofelia, Moreno, Lucas, Cho, Jaeho, Zeller, Bernward, Bovenschen, Niels, Grotzer, Michael, Alderete, Daniel, Snuderl, Matija, Zheludkova, Olga, et al, University of Zurich, and von Hoff, Katja

Subjects
2728 Neurology (clinical), 10036 Medical Clinic, 610 Medicine & health, 2730 Oncology, 1306 Cancer Research
Published
2021
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38. Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial

Author

Juhnke, B-Ole, Gessi, Marco, Gerber, Nicolas U, Friedrich, Carsten, Mynarek, Martin, von Bueren, André O, Haberler, Christine, Schüller, Ulrich, Kortmann, Rolf-Dieter, Timmermann, Beate, Bison, Brigitte, Warmuth-Metz, Monika, Kwiecien, Robert, Pfister, Stefan M, Spix, Claudia, Pietsch, Torsten, Kool, Marcel, Rutkowski, Stefan, von Hoff, Katja, Juhnke, B-Ole, Gessi, Marco, Gerber, Nicolas U, Friedrich, Carsten, Mynarek, Martin, von Bueren, André O, Haberler, Christine, Schüller, Ulrich, Kortmann, Rolf-Dieter, Timmermann, Beate, Bison, Brigitte, Warmuth-Metz, Monika, Kwiecien, Robert, Pfister, Stefan M, Spix, Claudia, Pietsch, Torsten, Kool, Marcel, Rutkowski, Stefan, and von Hoff, Katja

Abstract

Background. Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive tumors occurring in early childhood. Published clinical data refer to retrospective, heterogeneously treated cohorts. Here, we describe the outcome of patients treated according to the prospective P-HIT trial and subsequent HIT2000-interim-registry.Patients and methods. Age-stratified treatment included carboplatin/etoposide induction, tandem high-dose chemotherapy ("CARBO/ETO + HDCT"), and response-stratified radiotherapy. Patients with centrally reviewed neuropathological and molecularly confirmed diagnosis of ETMR recruited within the P-HIT trial (2001-2011; n = 19), the HIT2000-interim-registry (2012-2014; n = 12), and earlier HIT trials (n = 4) were selected for analysis.Results. Age-adjusted incidence rate was 1.35 per 1 million children (aged 1-4 years) in the years 2012-2014. Median age at diagnosis for 35 patients was 2.9 years. Metastases at diagnosis were detected in 9 patients. One patient died due to postoperative complications. For 30 patients with non-brainstem tumor location, 5-year progression-free survival (PFS) and overall survival (OS) were 35% and 47% after treatment with CARBO/ETO + HDCT (n = 17), compared to 0% and 8% with other treatments (n = 13, P[OS] = .011). All 4 patients with brainstem tumor died within 10 months after diagnosis. By multivariable analysis, supratentorial location: (HR [PFS]: 0.07 [95%CI: 0.01-0.38], P = .003), localized disease (M0): (HR [OS] M0, no residual tumor: 0.30 [95%CI: 0.009-1.09], P = .068; M0, residual tumor: 0.18 [95%CI: 0.04-0.76], P = .020), and CARBO/ETO + HDCT treatment (HR [OS]: 0.16 [95%CI: 0.05-054], P = .003) were identified as independent prognostic factors. Of 9 survivors, 6 were treated with radiotherapy (craniospinal 4; local 2).Conclusions. Our data indicate improved survival with intensified chemotherapy (CARBO/ETO + HDCT). However, despite intensive treatment, the outcome was poor. Thus, innovative therapies n

Published
2022

40. Abstract 2491: Molecular and clinical characterization of the new WHO entity ‘Astroblastoma, MN1 altered’ and its molecular subgroups

Author

Schmitt-Hoffner, Felix, primary, Gojo, Johannes, additional, Mauermann, Monika, additional, von Hoff, Katja, additional, Sill, Martin, additional, Korshunov, Andrey, additional, Stichel, Damian, additional, Sahm, Felix, additional, Jäger, Natalie, additional, Pfister, Stefan, additional, and Kool, Marcel, additional

Published
2022
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41. MEDB-37. Chemotherapy response prediction by molecular risk factors in metastatic childhood medulloblastoma

Author

Obrecht, Denise, primary, Bockmayr, Michael Ludwig, additional, Bison, Brigitte, additional, Pfister, Stefan M, additional, Sturm, Dominik, additional, Sahm, Felix, additional, Jones, David T W, additional, Sill, Martin, additional, von Hoff, Katja, additional, Benesch, Martin, additional, Gerber, Nicolas U, additional, von Bueren, André, additional, Friedrich, Carsten, additional, Pietsch, Torsten, additional, Schüller, Ulrich, additional, Mynarek, Martin, additional, and Rutkowski, Stefan, additional

Published
2022
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42. RARE-15. Astroblastoma, MN1 altered comprises two molecularly and clinically distinct subgroups defined by the fusion partners BEND2 and CXXC5

Author

Schmitt-Hoffner, Felix, primary, Gojo, Johannes, additional, Mauermann, Monika, additional, von Hoff, Katja, additional, Sill, Martin, additional, Stichel, Damian, additional, Capper, David, additional, Tauziede-Espariat, Arnault, additional, Varlet, Pascale, additional, Aldape, Kenneth, additional, Abdullaev, Zied, additional, Donson, Andrew M, additional, Schüller, Ulrich, additional, Snuderl, Matija, additional, Brandner, Sebastian, additional, Łastowska, Maria, additional, Trubicka, Joanna, additional, Miele, Evelina, additional, van der Lugt, Jasper, additional, Bunt, Jens, additional, Kramm, Christof, additional, Zapotocky, Michal, additional, Sahm, Felix, additional, Korshunov, Andrey, additional, Jäger, Natalie, additional, Pfister, Stefan M, additional, and Kool, Marcel, additional

Published
2022
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44. MEDB-14. Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome

Author

Kolodziejczak, Anna, primary, Guerrini-Rousseau, Lea, additional, Planchon, Julien Masliah, additional, Ecker, Jonas, additional, Selt, Florian, additional, Mynarek, Martin, additional, Obrecht, Denise, additional, Sill, Martin, additional, Hirsch, Steffen, additional, Sturm, Dominik, additional, Waszak, Sebastian M, additional, Ramaswamy, Vijay, additional, Pentikainen, Virve, additional, Demir, Haci Ahmet, additional, Clifford, Steven C, additional, Schwalbe, Ed, additional, Massimi, Luca, additional, Snuderl, Matija, additional, Galbraith, Kristyn, additional, Karajannis, Matthias A, additional, Hill, Katie, additional, Li, Bryan, additional, White, Christine L, additional, Redmond, Shelagh, additional, Loizos, Loizou, additional, Jakob, Marcus, additional, Kordes, Uwe, additional, Schmid, Irene, additional, Hauer, Julia, additional, Blattmann, Claudia, additional, Filippidou, Maria, additional, Scheurlen, Wolfram, additional, Kontny, Udo, additional, Grund, Kerstin, additional, Sutter, Christian, additional, Pietsch, Torsten, additional, van Tilburg, Cornelis M, additional, Frank, Stephan, additional, Schewe, Denis M, additional, Malkin, David, additional, Taylor, Michael D, additional, Tabori, Uri, additional, Bouffet, Eric, additional, Kool, Marcel, additional, Sahm, Felix, additional, von Deimling, Andreas, additional, Korshunov, Andrey, additional, Von Hoff, Katja, additional, Kratz, Christian, additional, Jones, David T W, additional, Rutkowski, Stefan, additional, Witt, Olaf, additional, Bougeard, Gaelle, additional, Pajtler, Kristian W, additional, Pfister, Stefan M, additional, Bourdeaut, Franck, additional, and Milde, Till, additional

Published
2022
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45. RONC-16. Proton therapy for patients with embryonal tumor with multilayered rosettes in early childhood – results of the prospective KiProReg Study

Author

Peters, Sarah, primary, Frisch, Sabine, additional, Merta, Julien, additional, Bäumer, Christian, additional, Blase, Christoph, additional, Tippelt, Stephan, additional, von Zezschwitz, Barbara, additional, Johann, Pascal, additional, von Hoff, Katja, additional, Geismar, Dirk, additional, and Timmermann, Beate, additional

Published
2022
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46. QOL-10. Treatment-induced leukoencephalopathy in pediatric medulloblastoma survivors and its impact on long-term neurocognitive functioning

Author

Wägner, Lukas, primary, Bison, Brigitte, additional, Neumann-Holbeck, Anne, additional, Tischler, Tanja, additional, Guiard, Anika, additional, Obrecht, Denise, additional, Ottensmeier, Holger, additional, Kortmann, Rolf-Dieter, additional, von Hoff, Katja, additional, Schlegel, Paul-Gerhardt, additional, Remke, Marc, additional, Redlich, Antje, additional, Holzer, Ursula, additional, Blattmann, Claudia, additional, Fleischhack, Gudrun, additional, Sander, Annette, additional, Jorch, Norbert, additional, Becker, Martina, additional, Karremann, Michael, additional, Frühwald, Michael C, additional, van Buiren, Miriam, additional, Struve, Nina, additional, Warmuth-Metz, Monika, additional, Rutkowski, Stefan, additional, and Mynarek, Martin, additional

Published
2022
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47. MEDB-04. Young children with metastatic medulloblastoma: frequent requirement for radiotherapy in children with non-WNT/non-SHH medulloblastoma despite highly intensified chemotherapy – Results of the MET-HIT2000-BIS4 trial

Author

Mynarek, Martin, primary, Goschzik, Tobias, additional, Kool, Marcel, additional, von Hoff, Katja, additional, Ottensmeier, Holger, additional, Warmuth-Metz, Monika, additional, Bison, Brigitte, additional, Sill, Martin, additional, Rushing, Elisabeth Jane, additional, Hasselblatt, Martin, additional, Koch, Arend, additional, Schüller, Ulrich, additional, von Deimling, Andreas, additional, Riemenschneider, Markus J, additional, Dohmen, Hildegard, additional, Monoranu, Camelia-Maria, additional, Sommer, Clemens, additional, Staszewski, Ori, additional, Mawrin, Christian, additional, Schittenhelm, Jens, additional, Brück, Wolfgang, additional, Filipski, Katharina, additional, Hartmann, Christian, additional, Meinhardt, Matthias, additional, Pietschmann, Klaus, additional, Haberler, Christine, additional, Slavc, Irene, additional, Gerber, Nicolas U, additional, Grotzer, Michael, additional, Benesch, Martin, additional, Schlegel, Paul-Gerhardt, additional, Deinlein, Frank, additional, Bode, Udo, additional, von Bueren, André O, additional, Friedrich, Carsten, additional, Obrecht, Denise, additional, Fleischhack, Gudrun, additional, Kwiecien, Robert, additional, Faldum, Andreas, additional, Kortmann, Rolf-Dieter, additional, Pietsch, Torsten, additional, Pfister, Stefan, additional, and Rutkowski, Stefan, additional

Published
2022
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48. ETMR-06. Molecular and clinical characteristics of CNS tumors withBCOR(L1) fusion/internal tandem duplication

Author

Gojo, Johannes, primary, Schmitt-Hoffner, Felix, additional, Mauermann, Monika, additional, von Hoff, Katja, additional, Sill, Martin, additional, Korshunov, Andrey, additional, Stichel, Damian, additional, Capper, David, additional, Tauziede-Espariat, Arnault, additional, Varlet, Pascale, additional, Aldape, Kenneth, additional, Abdullaev, Zied, additional, Donson, Andrew, additional, Pahnke, Jens, additional, Schüller, Ulrich, additional, Tran, Ivy, additional, Galbraith, Kristyn, additional, Snuderl, Matija, additional, Alexandrescu, Sanda, additional, Brandner, Sebastian, additional, Łastowska, Maria, additional, Miele, Evelina, additional, Lugt, Jasper v, additional, Meijer, Lisethe, additional, Bunt, Jens, additional, Kramm, Christof, additional, Hansford, Jordan R, additional, Krskova, Lenka, additional, Zapotocky, Michal, additional, Nobusawa, Sumihito, additional, Solomon, David, additional, Haberler, Christine, additional, Jones, Barbara, additional, Sturm, Dominik, additional, Sahm, Felix, additional, Jäger, Natalie, additional, Pfister, Stefan M, additional, and Kool, Marcel, additional

Published
2022
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49. Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome

Author

Kolodziejczak, Anna, Guerrini-Rousseau, Lea, Planchon, Julien Masliah, Ecker, Jonas, Selt, Florian, Mynarek, Martin, Obrecht, Denise, Sill, Martin, Hirsch, Steffen, Sturm, Dominik, Waszak, Sebastian M., Ramaswamy, Vijay, Pentikainen, Virve, Demir, Haci Ahmet, Clifford, Steven C., Schwalbe, Ed, Massimi, Luca, Snuderl, Matija, Galbraith, Kristyn, Karajannis, Matthias A., Hill, Katie, Li, Bryan, White, Christine L., Redmond, Shelagh, Loizos, Loizou, Jakob, Marcus, Kordes, Uwe, Schmid, Irene, Hauer, Julia, Blattmann, Claudia, Filippidou, Maria, Scheurlen, Wolfram, Kontny, Hans Udo, Grund, Kerstin, Sutter, Christian, Pietsch, Torsten, van Tilburg, Cornelis M., Frank, Stephan, Schewe, Denis M., Malkin, David, Taylor, Michael D., Tabori, Uri, Bouffet, Eric, Kool, Marcel, Sahm, Felix, Von Deimling, Andreas, Korshunov, Andrey, Von Hoff, Katja, Kratz, Christian, Jones, David T. W., Rutkowski, Stefan, Witt, Olaf, Bougeard, Gaelle, Pajtler, Kristian W., Pfister, Stefan M., Bourdeaut, Franck, and Milde, Till

Abstract

20. International Symposium on Pediatric Neuro-Oncology, ISPNO 2022, Hamburg, Germany, 12 Jun 2022 - 15 Jun 2022; Neuro-Oncology : official journal of the World Federation of Neuro-Oncology 24(Supplement_1), MEDB-14 (2022). doi:10.1093/neuonc/noac079.389 special issue: "Abstracts from the 20th International Symposium on Pediatric Neuro-Oncology (ISPNO 2022)", Published by Oxford Univ. Press, Oxford

Published
2022
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50. Evidence of H3 K27M mutations in posterior fossa ependymomas

Author

Gessi, Marco, Capper, David, Sahm, Felix, Huang, Kristin, von Deimling, Andreas, Tippelt, Stephan, Fleischhack, Gudrun, Scherbaum, Daniel, Alfer, Joachim, Juhnke, Björn-Ole, von Hoff, Katja, Rutkowski, Stefan, Warmuth-Metz, Monika, Chavez, Lukas, Pfister, Stefan M., Pietsch, Torsten, Jones, David T. W., and Sturm, Dominik

Published
2016
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