Search

Your search keyword '"Sill, Martin"' showing total 744 results
Start Over Author "Sill, Martin"
744 results on '"Sill, Martin"'

1. Multi-omic and single-cell profiling of chromothriptic medulloblastoma reveals genomic and transcriptomic consequences of genome instability

Author

Smirnov, Petr, Przybilla, Moritz J., Simovic-Lorenz, Milena, Parra, R. Gonzalo, Susak, Hana, Ratnaparkhe, Manasi, Wong, John KL., Körber, Verena, Mallm, Jan-Philipp, Philippos, George, Sill, Martin, Kolb, Thorsten, Kumar, Rithu, Casiraghi, Nicola, Okonechnikov, Konstantin, Ghasemi, David R., Maaß, Kendra Korinna, Pajtler, Kristian W., Jauch, Anna, Korshunov, Andrey, Höfer, Thomas, Zapatka, Marc, Pfister, Stefan M., Huber, Wolfgang, Stegle, Oliver, and Ernst, Aurélie

Published
2024
Full Text
View/download PDF

2. EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics

Author

Hench, Jürgen, Hultschig, Claus, Brugger, Jon, Mariani, Luigi, Guzman, Raphael, Soleman, Jehuda, Leu, Severina, Benton, Miles, Stec, Irenäus Maria, Hench, Ivana Bratic, Hoffmann, Per, Harter, Patrick, Weber, Katharina J, Albers, Anne, Thomas, Christian, Hasselblatt, Martin, Schüller, Ulrich, Restelli, Lisa, Capper, David, Hewer, Ekkehard, Diebold, Joachim, Kolenc, Danijela, Schneider, Ulf C., Rushing, Elisabeth, della Monica, Rosa, Chiariotti, Lorenzo, Sill, Martin, Schrimpf, Daniel, von Deimling, Andreas, Sahm, Felix, Kölsche, Christian, Tolnay, Markus, and Frank, Stephan

Published
2024
Full Text
View/download PDF

3. Clinical and molecular study of radiation-induced gliomas

Author

Trkova, Katerina, Sumerauer, David, Bubenikova, Adela, Krskova, Lenka, Vicha, Ales, Koblizek, Miroslav, Zamecnik, Josef, Jurasek, Bruno, Kyncl, Martin, Malinova, Bela, Ondrova, Barbora, Jones, David T. W., Sill, Martin, Strnadova, Martina, Stolova, Lucie, Misove, Adela, Benes, III, Vladimir, and Zapotocky, Michal

Published
2024
Full Text
View/download PDF

4. 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. Genetical and epigenetical profiling identifies two subgroups of pineal parenchymal tumors of intermediate differentiation (PPTID) with distinct molecular, histological and clinical characteristics

Author

Rahmanzade, Ramin, Pfaff, Elke, Banan, Rouzbeh, Sievers, Philipp, Suwala, Abigail K., Hinz, Felix, Bogumil, Henri, Cherkezov, Asan, Kaan, Aras Fuat, Schrimpf, Daniel, Friedel, Dennis, Göbel, Kirsten, Keller, Felix, Saenz-Sardà, Xavier, Lossos, Alexander, Sill, Martin, Witt, Olaf, Sakowitz, Oliver W., Korshunov, Andrey, Reuss, David E., Etminan, Nima, Unterberg, Andreas, Ratliff, Miriam, Herold-Mende, Christel, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., and Sahm, Felix

Published
2023
Full Text
View/download PDF

6. Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions

Author

Bogumil, Henri, Sill, Martin, Schrimpf, Daniel, Ismer, Britta, Blume, Christina, Rahmanzade, Ramin, Hinz, Felix, Cherkezov, Asan, Banan, Rouzbeh, Friedel, Dennis, Reuss, David E., Selt, Florian, Ecker, Jonas, Milde, Till, Pajtler, Kristian W., Schittenhelm, Jens, Hench, Jürgen, Frank, Stephan, Boldt, Henning B., Kristensen, Bjarne Winther, Scheie, David, Melchior, Linea C., Olesen, Viola, Sehested, Astrid, Boué, Daniel R., Abdullaev, Zied, Satgunaseelan, Laveniya, Kurth, Ina, Seidlitz, Annekatrin, White, Christine L., Ng, Ho-Keung, Shi, Zhi-Feng, Haberler, Christine, Deckert, Martina, Timmer, Marco, Goldbrunner, Roland, Tauziède-Espariat, Arnault, Varlet, Pascale, Brandner, Sebastian, Alexandrescu, Sanda, Snuderl, Matija, Aldape, Kenneth, Korshunov, Andrey, Witt, Olaf, Herold-Mende, Christel, Unterberg, Andreas, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., Sahm, Felix, and Sievers, Philipp

Published
2023
Full Text
View/download PDF

7. Molecular characterisation defines clinically-actionable heterogeneity within Group 4 medulloblastoma and improves disease risk-stratification

Author

Goddard, Jack, Castle, Jemma, Southworth, Emily, Fletcher, Anya, Crosier, Stephen, Martin-Guerrero, Idoia, García-Ariza, Miguel, Navajas, Aurora, Masliah-Planchon, Julien, Bourdeaut, Franck, Dufour, Christelle, Ayrault, Olivier, Goschzik, Tobias, Pietsch, Torsten, Sill, Martin, Pfister, Stefan M., Rutkowski, Stefan, Richardson, Stacey, Hill, Rebecca M., Williamson, Daniel, Bailey, Simon, Schwalbe, Edward C., Clifford, Steven C., and Hicks, Debbie

Published
2023
Full Text
View/download PDF

8. Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology

Author

Sturm, Dominik, Capper, David, Andreiuolo, Felipe, Gessi, Marco, Kölsche, Christian, Reinhardt, Annekathrin, Sievers, Philipp, Wefers, Annika K., Ebrahimi, Azadeh, Suwala, Abigail K., Gielen, Gerrit H., Sill, Martin, Schrimpf, Daniel, Stichel, Damian, Hovestadt, Volker, Daenekas, Bjarne, Rode, Agata, Hamelmann, Stefan, Previti, Christopher, Jäger, Natalie, Buchhalter, Ivo, Blattner-Johnson, Mirjam, Jones, Barbara C., Warmuth-Metz, Monika, Bison, Brigitte, Grund, Kerstin, Sutter, Christian, Hirsch, Steffen, Dikow, Nicola, Hasselblatt, Martin, Schüller, Ulrich, Koch, Arend, Gerber, Nicolas U., White, Christine L., Buntine, Molly K., Kinross, Kathryn, Algar, Elizabeth M., Hansford, Jordan R., Gottardo, Nicholas G., Schuhmann, Martin U., Thomale, Ulrich W., Hernáiz Driever, Pablo, Gnekow, Astrid, Witt, Olaf, Müller, Hermann L., Calaminus, Gabriele, Fleischhack, Gudrun, Kordes, Uwe, Mynarek, Martin, Rutkowski, Stefan, Frühwald, Michael C., Kramm, Christof M., von Deimling, Andreas, Pietsch, Torsten, Sahm, Felix, Pfister, Stefan M., and Jones, David. T. W.

Published
2023
Full Text
View/download PDF

9. 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
Full Text
View/download PDF

10. Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures

Author

Schoof, Melanie, Godbole, Shweta, Albert, Thomas K., Dottermusch, Matthias, Walter, Carolin, Ballast, Annika, Qin, Nan, Olivera, Marlena Baca, Göbel, Carolin, Neyazi, Sina, Holdhof, Dörthe, Kresbach, Catena, Peter, Levke-Sophie, Epplen, Gefion Dorothea, Thaden, Vanessa, Spohn, Michael, Blattner-Johnson, Mirjam, Modemann, Franziska, Mynarek, Martin, Rutkowski, Stefan, Sill, Martin, Varghese, Julian, Afflerbach, Ann-Kristin, Eckhardt, Alicia, Münter, Daniel, Verma, Archana, Struve, Nina, Jones, David T. W., Remke, Marc, Neumann, Julia E., Kerl, Kornelius, and Schüller, Ulrich

Published
2023
Full Text
View/download PDF

11. Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours

Author

Nabbi, Arash, Beck, Pengbo, Delaidelli, Alberto, Oldridge, Derek A., Sudhaman, Sumedha, Zhu, Kelsey, Yang, S. Y. Cindy, Mulder, David T., Bruce, Jeffrey P., Paulson, Joseph N., Raman, Pichai, Zhu, Yuankun, Resnick, Adam C., Sorensen, Poul H., Sill, Martin, Brabetz, Sebastian, Lambo, Sander, Malkin, David, Johann, Pascal D., Kool, Marcel, Jones, David T. W., Pfister, Stefan M., Jäger, Natalie, and Pugh, Trevor J.

Published
2023
Full Text
View/download PDF

12. Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature

Author

Sievers, Philipp, Sill, Martin, Schrimpf, Daniel, Abdullaev, Zied, Donson, Andrew M., Lake, Jessica A., Friedel, Dennis, Scheie, David, Tynninen, Olli, Rauramaa, Tuomas, Vepsäläinen, Kaisa L., Samuel, David, Chapman, Rebecca, Grundy, Richard G., Pajtler, Kristian W., Tauziède-Espariat, Arnault, Métais, Alice, Varlet, Pascale, Snuderl, Matija, Jacques, Thomas S., Aldape, Kenneth, Reuss, David E., Korshunov, Andrey, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Sahm, Felix, and Jones, David T. W.

Published
2023
Full Text
View/download PDF

13. Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1

Author

Suwala, Abigail K, Stichel, Damian, Schrimpf, Daniel, Maas, Sybren LN, Sill, Martin, Dohmen, Hildegard, Banan, Rouzbeh, Reinhardt, Annekathrin, Sievers, Philipp, Hinz, Felix, Blattner-Johnson, Mirjam, Hartmann, Christian, Schweizer, Leonille, Boldt, Henning B, Kristensen, Bjarne Winther, Schittenhelm, Jens, Wood, Matthew D, Chotard, Guillaume, Bjergvig, Rolf, Das, Anirban, Tabori, Uri, Hasselblatt, Martin, Korshunov, Andrey, Abdullaev, Zied, Quezado, Martha, Aldape, Kenneth, Harter, Patrick N, Snuderl, Matija, Hench, Jürgen, Frank, Stephan, Acker, Till, Brandner, Sebastian, Winkler, Frank, Wesseling, Pieter, Pfister, Stefan M, Reuss, David E, Wick, Wolfgang, von Deimling, Andreas, Jones, David TW, and Sahm, Felix

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Human Genome, Brain Cancer, Neurosciences, Cancer, Rare Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, Brain Neoplasms, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 7, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, DNA Methylation, Female, Gene Deletion, Glial Fibrillary Acidic Protein, Glioblastoma, Humans, Male, Middle Aged, Neuroectodermal Tumors, Primitive, PTEN Phosphohydrolase, Retinoblastoma Binding Proteins, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, GBM, PNET, DNA methylation, Phenotype, Classification, Plasticity, Neurology & Neurosurgery
Abstract

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

Published
2021

14. Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1

Author

Sievers, Philipp, Sill, Martin, Blume, Christina, Tauziede-Espariat, Arnault, Schrimpf, Daniel, Stichel, Damian, Reuss, David E, Dogan, Helin, Hartmann, Christian, Mawrin, Christian, Hasselblatt, Martin, Stummer, Walter, Schick, Uta, Hench, Jürgen, Frank, Stephan, Ketter, Ralf, Schweizer, Leonille, Schittenhelm, Jens, Puget, Stéphanie, Brandner, Sebastian, Jaunmuktane, Zane, Küsters, Benno, Abdullaev, Zied, Pekmezci, Melike, Snuderl, Matija, Ratliff, Miriam, Herold-Mende, Christel, Unterberg, Andreas, Aldape, Kenneth, Ellison, David W, Wesseling, Pieter, Reifenberger, Guido, Wick, Wolfgang, Perry, Arie, Varlet, Pascale, Pfister, Stefan M, Jones, David TW, von Deimling, Andreas, and Sahm, Felix

Subjects
Human Genome, Brain Disorders, Pediatric, Cancer, Genetics, Rare Diseases, Brain Cancer, Aetiology, 2.1 Biological and endogenous factors, Brain Neoplasms, Child, Chromosomal Proteins, Non-Histone, Cohort Studies, DNA Methylation, DNA Mutational Analysis, DNA, Neoplasm, DNA-Binding Proteins, Disease Progression, Epigenesis, Genetic, Female, Genome-Wide Association Study, Humans, Immunohistochemistry, Male, Meningioma, Mutation, Neoplasm Recurrence, Local, Treatment Outcome, Young Adult, Brain tumor, Clear cell, SMARCE1, DNA methylation profile, German Consortium “Aggressive Meningiomas”, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Clear cell meningioma represents an uncommon variant of meningioma that typically affects children and young adults. Although an enrichment of loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset of tumors (n = 31), initially identified through genome-wide DNA methylation screening among a cohort of 3093 meningiomas, of which most were diagnosed histologically as clear cell meningioma. This cohort was further supplemented by an additional 11 histologically diagnosed clear cell meningiomas for analysis (n = 42). Targeted DNA sequencing revealed SMARCE1 mutations in 33/34 analyzed samples, accompanied by a nuclear loss of expression determined via immunohistochemistry and a decreased SMARCE1 transcript expression in the tumor cells. Analysis of time to progression or recurrence of patients within the clear cell meningioma group (n = 14) in comparison to those with meningioma WHO grade 2 (n = 220) revealed a similar outcome and support the assignment of WHO grade 2 to these tumors. Our findings indicate the existence of a highly distinct epigenetic signature of clear cell meningiomas, separate from all other variants of meningiomas, with recurrent mutations in the SMARCE1 gene. This suggests that these tumors may arise from a different precursor cell population than the broad spectrum of the other meningioma subtypes.

Published
2021

15. A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR.

Author

Sievers, Philipp, Sill, Martin, Schrimpf, Daniel, Stichel, Damian, Reuss, David E, Sturm, Dominik, Hench, Jürgen, Frank, Stephan, Krskova, Lenka, Vicha, Ales, Zapotocky, Michal, Bison, Brigitte, Castel, David, Grill, Jacques, Debily, Marie-Anne, Harter, Patrick N, Snuderl, Matija, Kramm, Christof M, Reifenberger, Guido, Korshunov, Andrey, Jabado, Nada, Wesseling, Pieter, Wick, Wolfgang, Solomon, David A, Perry, Arie, Jacques, Thomas S, Jones, Chris, Witt, Olaf, Pfister, Stefan M, von Deimling, Andreas, Jones, David TW, and Sahm, Felix

Subjects
Brain Disorders, Pediatric Cancer, Cancer, Pediatric, Brain Cancer, Rare Diseases, Genetics, Neurosciences, Brain Neoplasms, Child, DNA Methylation, ErbB Receptors, Genes, erbB-1, Glioma, Histones, Humans, Mutation, Thalamus, (bi)thalamic, EGFR mutation, H3 K27M mutation, K27me3, pediatric-type high-grade glioma, EGFR mutation, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundMalignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern.MethodsHere, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas.ResultsEGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations.ConclusionsOur findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.

Published
2021

16. Author Correction: Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology

Author

Sturm, Dominik, Capper, David, Andreiuolo, Felipe, Gessi, Marco, Kölsche, Christian, Reinhardt, Annekathrin, Sievers, Philipp, Wefers, Annika K., Ebrahimi, Azadeh, Suwala, Abigail K., Gielen, Gerrit H., Sill, Martin, Schrimpf, Daniel, Stichel, Damian, Hovestadt, Volker, Daenekas, Bjarne, Rode, Agata, Hamelmann, Stefan, Previti, Christopher, Jäger, Natalie, Buchhalter, Ivo, Blattner-Johnson, Mirjam, Jones, Barbara C., Warmuth-Metz, Monika, Bison, Brigitte, Grund, Kerstin, Sutter, Christian, Hirsch, Steffen, Dikow, Nicola, Hasselblatt, Martin, Schüller, Ulrich, Koch, Arend, Gerber, Nicolas U., White, Christine L., Buntine, Molly K., Kinross, Kathryn, Algar, Elizabeth M., Hansford, Jordan R., Gottardo, Nicholas G., Schuhmann, Martin U., Thomale, Ulrich W., Hernáiz Driever, Pablo, Gnekow, Astrid, Witt, Olaf, Müller, Hermann L., Calaminus, Gabriele, Fleischhack, Gudrun, Kordes, Uwe, Mynarek, Martin, Rutkowski, Stefan, Frühwald, Michael C., Kramm, Christof M., von Deimling, Andreas, Pietsch, Torsten, Sahm, Felix, Pfister, Stefan M., and Jones, David. T. W.

Published
2024
Full Text
View/download PDF

17. 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
Full Text
View/download PDF

18. Epigenetic profiling reveals a subset of pediatric-type glioneuronal tumors characterized by oncogenic gene fusions involving several targetable kinases

Author

Sievers, Philipp, Sill, Martin, Schrimpf, Daniel, Friedel, Dennis, Sturm, Dominik, Gardberg, Maria, Kurian, Kathreena M., Krskova, Lenka, Vicha, Ales, Schaller, Tina, Hagel, Christian, Abdullaev, Zied, Aldape, Kenneth, Jacques, Thomas S., Korshunov, Andrey, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., and Sahm, Felix

Published
2022
Full Text
View/download PDF

19. Molecular diagnostics enables detection of actionable targets: the Pediatric Targeted Therapy 2.0 registry

Author

Ecker, Jonas, Selt, Florian, Sturm, Dominik, Sill, Martin, Korshunov, Andrey, Hirsch, Steffen, Capper, David, Dikow, Nicola, Sutter, Christian, Müller, Carina, Sigaud, Romain, Eggert, Angelika, Simon, Thorsten, Niehues, Tim, von Deimling, Andreas, Pajtler, Kristian W., van Tilburg, Cornelis M., Jones, David T.W., Sahm, Felix, Pfister, Stefan M., Witt, Olaf, and Milde, Till

Published
2023
Full Text
View/download PDF

20. Integrated genomic analysis reveals actionable targets in pediatric spinal cord low-grade gliomas

Author

Misove Adela, Vicha Ales, Broz Petr, Vanova Katerina, Sumerauer David, Stolova Lucie, Sramkova Lucie, Koblizek Miroslav, Zamecnik Josef, Kyncl Martin, Holubova Zuzana, Liby Petr, Taborsky Jakub, Benes Vladimir, Pernikova Ivana, Jones T. W. David, Sill Martin, Stancokova Terezia, Krskova Lenka, and Zapotocky Michal

Subjects
Spinal cord, Low-grade glioma, KIAA1549:BRAF fusion, NTRK fusion, Methylation profiling, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Gliomas are the most common central nervous tumors in children and adolescents. However, spinal cord low-grade gliomas (sLGGs) are rare, with scarce information on tumor genomics and epigenomics. To define the molecular landscape of sLGGs, we integrated clinical data, histology, and multi-level genetic and epigenetic analyses on a consecutive cohort of 26 pediatric patients. Driver molecular alteration was found in 92% of patients (24/26). A novel variant of KIAA1549:BRAF fusion (ex10:ex9) was identified using RNA-seq in four cases. Importantly, only one-third of oncogenic drivers could be revealed using standard diagnostic methods, and two-thirds of pediatric patients with sLGGs required extensive molecular examination. The majority (23/24) of detected alterations were potentially druggable targets. Four patients in our cohort received targeted therapy with MEK or NTRK inhibitors. Three of those exhibited clinical improvement (two with trametinib, one with larotrectinib), and two patients achieved partial response. Methylation profiling was implemented to further refine the diagnosis and revealed intertumoral heterogeneity in sLGGs. Although 55% of tumors clustered with pilocytic astrocytoma, other rare entities were identified in this patient population. In particular, diffuse leptomeningeal glioneuronal tumors (n = 3) and high-grade astrocytoma with piloid features (n = 1) and pleomorphic xanthoastrocytoma (n = 1) were present. A proportion of tumors (14%) had no match with the current version of the classifier. Complex molecular genetic sLGGs characterization was invaluable to refine diagnosis, which has proven to be essential in such a rare tumor entity. Moreover, identifying a high proportion of drugable targets in sLGGs opened an opportunity for new treatment modalities.

Published
2022
Full Text
View/download PDF

21. Rapid-CNS2: rapid comprehensive adaptive nanopore-sequencing of CNS tumors, a proof-of-concept study

Author

Patel, Areeba, Dogan, Helin, Payne, Alexander, Krause, Elena, Sievers, Philipp, Schoebe, Natalie, Schrimpf, Daniel, Blume, Christina, Stichel, Damian, Holmes, Nadine, Euskirchen, Philipp, Hench, Jürgen, Frank, Stephan, Rosenstiel-Goidts, Violaine, Ratliff, Miriam, Etminan, Nima, Unterberg, Andreas, Dieterich, Christoph, Herold-Mende, Christel, Pfister, Stefan M., Wick, Wolfgang, Loose, Matthew, von Deimling, Andreas, Sill, Martin, Jones, David T. W., Schlesner, Matthias, and Sahm, Felix

Published
2022
Full Text
View/download PDF

22. Heterogeneity within the PF-EPN-B ependymoma subgroup

Author

Cavalli, Florence MG, Hübner, Jens-Martin, Sharma, Tanvi, Luu, Betty, Sill, Martin, Zapotocky, Michal, Mack, Stephen C, Witt, Hendrik, Lin, Tong, Shih, David JH, Ho, Ben, Santi, Mariarita, Emery, Lyndsey, Hukin, Juliette, Dunham, Christopher, McLendon, Roger E, Lipp, Eric S, Gururangan, Sridharan, Grossbach, Andrew, French, Pim, Kros, Johan M, van Veelen, Marie-Lise C, Rao, Amulya A Nageswara, Giannini, Caterina, Leary, Sarah, Jung, Shin, Faria, Claudia C, Mora, Jaume, Schüller, Ulrich, Alonso, Marta M, Chan, Jennifer A, Klekner, Almos, Chambless, Lola B, Hwang, Eugene I, Massimino, Maura, Eberhart, Charles G, Karajannis, Matthias A, Lu, Benjamin, Liau, Linda M, Zollo, Massimo, Ferrucci, Veronica, Carlotti, Carlos, Tirapelli, Daniela PC, Tabori, Uri, Bouffet, Eric, Ryzhova, Marina, Ellison, David W, Merchant, Thomas E, Gilbert, Mark R, Armstrong, Terri S, Korshunov, Andrey, Pfister, Stefan M, Taylor, Michael D, Aldape, Kenneth, Pajtler, Kristian W, Kool, Marcel, and Ramaswamy, Vijay

Subjects
Genetics, Cancer, Clinical Research, Rare Diseases, Human Genome, Brain Cancer, Brain Disorders, Adolescent, Adult, Age Factors, Child, Cohort Studies, DNA Copy Number Variations, DNA Methylation, Ependymoma, Female, Gene Expression Profiling, Humans, Infratentorial Neoplasms, Kaplan-Meier Estimate, Male, Microarray Analysis, Middle Aged, Young Adult, Posterior fossa, Subgrouping, PFB, PFA, Clustering, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.

Published
2018

23. 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

24. Correction to: Integrated genomic analysis reveals actionable targets in pediatric spinal cord low-grade gliomas

Author

Misove, Adela, Vicha, Ales, Broz, Petr, Vanova, Katerina, Sumerauer, David, Stolova, Lucie, Sramkova, Lucie, Koblizek, Miroslav, Zamecnik, Josef, Kyncl, Martin, Holubova, Zuzana, Liby, Petr, Taborsky, Jakub, Benes, III, Vladimir, Pernikova, Ivana, Jones, David T. W., Sill, Martin, Stancokova, Terezia, Krskova, Lenka, and Zapotocky, Michal

Published
2022
Full Text
View/download PDF

25. DNA methylation-based classification of sinonasal tumors

Author

Jurmeister, Philipp, Glöß, Stefanie, Roller, Renée, Leitheiser, Maximilian, Schmid, Simone, Mochmann, Liliana H., Payá Capilla, Emma, Fritz, Rebecca, Dittmayer, Carsten, Friedrich, Corinna, Thieme, Anne, Keyl, Philipp, Jarosch, Armin, Schallenberg, Simon, Bläker, Hendrik, Hoffmann, Inga, Vollbrecht, Claudia, Lehmann, Annika, Hummel, Michael, Heim, Daniel, Haji, Mohamed, Harter, Patrick, Englert, Benjamin, Frank, Stephan, Hench, Jürgen, Paulus, Werner, Hasselblatt, Martin, Hartmann, Wolfgang, Dohmen, Hildegard, Keber, Ursula, Jank, Paul, Denkert, Carsten, Stadelmann, Christine, Bremmer, Felix, Richter, Annika, Wefers, Annika, Ribbat-Idel, Julika, Perner, Sven, Idel, Christian, Chiariotti, Lorenzo, Della Monica, Rosa, Marinelli, Alfredo, Schüller, Ulrich, Bockmayr, Michael, Liu, Jacklyn, Lund, Valerie J., Forster, Martin, Lechner, Matt, Lorenzo-Guerra, Sara L., Hermsen, Mario, Johann, Pascal D., Agaimy, Abbas, Seegerer, Philipp, Koch, Arend, Heppner, Frank, Pfister, Stefan M., Jones, David T. W., Sill, Martin, von Deimling, Andreas, Snuderl, Matija, Müller, Klaus-Robert, Forgó, Erna, Howitt, Brooke E., Mertins, Philipp, Klauschen, Frederick, and Capper, David

Published
2022
Full Text
View/download PDF

26. Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

Author

Peterziel, Heike, Jamaladdin, Nora, ElHarouni, Dina, Gerloff, Xenia F., Herter, Sonja, Fiesel, Petra, Berker, Yannick, Blattner-Johnson, Mirjam, Schramm, Kathrin, Jones, Barbara C., Reuss, David, Turunen, Laura, Friedenauer, Aileen, Holland-Letz, Tim, Sill, Martin, Weiser, Lena, Previti, Christopher, Balasubramanian, Gnanaprakash, Gerber, Nicolas U., Gojo, Johannes, Hutter, Caroline, Øra, Ingrid, Lohi, Olli, Kattamis, Antonis, de Wilde, Bram, Westermann, Frank, Tippelt, Stephan, Graf, Norbert, Nathrath, Michaela, Sparber-Sauer, Monika, Sehested, Astrid, Kramm, Christof M., Dirksen, Uta, Kallioniemi, Olli, Pfister, Stefan M., van Tilburg, Cornelis M., Jones, David T. W., Saarela, Jani, Pietiäinen, Vilja, Jäger, Natalie, Schlesner, Matthias, Kopp-Schneider, Annette, Oppermann, Sina, Milde, Till, Witt, Olaf, and Oehme, Ina

Published
2022
Full Text
View/download PDF

27. Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival

Author

Ebrahimi, Azadeh, Korshunov, Andrey, Reifenberger, Guido, Capper, David, Felsberg, Joerg, Trisolini, Elena, Pollo, Bianca, Calatozzolo, Chiara, Prinz, Marco, Staszewski, Ori, Schweizer, Leonille, Schittenhelm, Jens, Harter, Patrick N., Paulus, Werner, Thomas, Christian, Kohlhof-Meinecke, Patricia, Seiz-Rosenhagen, Marcel, Milde, Till, Casalini, Belén M., Suwala, Abigail, Wefers, Annika K., Reinhardt, Annekathrin, Sievers, Philipp, Kramm, Christof M., Etminam, Nima, Unterberg, Andreas, Wick, Wolfgang, Herold-Mende, Christel, Sturm, Dominik, Pfister, Stefan M., Sill, Martin, Jones, David T. W., Schrimpf, Daniel, Reuss, David E., Aldape, Ken, Abdullaev, Zied, Sahm, Felix, von Deimling, Andreas, and Stichel, Damian

Published
2022
Full Text
View/download PDF

28. Versatile, accessible cross-platform molecular profiling of central nervous system tumors: web-based, prospective multi-center validation

Author

Sahm, Felix, primary, Patel, Areeba, additional, Göbel, Kirsten, additional, Hinz, Felix, additional, Ille, Sebastian, additional, Dogan, Helin, additional, Lomakin, Artem, additional, Schrimpf, Daniel, additional, Göller, Pauline, additional, Ritter, Michael, additional, Kerbs, Paul, additional, Pfeifer, Lisa, additional, Schoebe, Natalie, additional, Hamelmann, Stefan, additional, Blume, Christina, additional, Bogumil, Henri, additional, Berghaus, Natalie, additional, Euskirchen, Philipp, additional, Schweizer, Leonille, additional, Hultschig, Claus, additional, Roy, Nadine Van, additional, Dorpe, Jo Van, additional, Meulen, Joni Van der, additional, Loontiens, Siebe, additional, Dedeurwaerdere, Franceska, additional, Leske, Henning, additional, Halldorsson, Skarphedinn, additional, Fox, Graeme, additional, Deacon, Simon, additional, Cahyani, Inswasti, additional, Holmes, Nadine, additional, Wibowo, Satrio, additional, Munro, Rory, additional, Martin, Dan, additional, Sharif, Abid, additional, Housley, Mark, additional, Goldspring, Robert, additional, Brandner, Sebastian, additional, Roy, Somak, additional, Hench, Jürgen, additional, Frank, Stephan, additional, Unterberg, Andreas, additional, Goidts, Violaine, additional, Jäger, Natalie, additional, Paine, Simon, additional, Smith, Stuart, additional, Herold-Mende, Christel, additional, Wick, Wolfgang, additional, Pfister, Stefan, additional, Krieg, Sandro, additional, Vik-Mo, Einar, additional, von Deimling, Andreas, additional, Jones, David, additional, Loose, Matthew, additional, Schlesner, Matthias, additional, and Sill, Martin, additional

Published
2024
Full Text
View/download PDF

29. GOPC:ROS1 and other ROS1 fusions represent a rare but recurrent drug target in a variety of glioma types

Author

Sievers, Philipp, Stichel, Damian, Sill, Martin, Schrimpf, Daniel, Sturm, Dominik, Selt, Florian, Ecker, Jonas, Kazdal, Daniel, Miele, Evelina, Kranendonk, Mariëtte E. G., Tops, Bastiaan B. J., Kohlhof-Meinecke, Patricia, Beschorner, Rudi, Kramm, Christof M., Hasselblatt, Martin, Reifenberger, Guido, Capper, David, Wesseling, Pieter, Stenzinger, Albrecht, Milde, Till, Korshunov, Andrey, Witt, Olaf, Pfister, Stefan M., Wick, Wolfgang, von Deimling, Andreas, Jones, David T. W., and Sahm, Felix

Published
2021
Full Text
View/download PDF

30. 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
Full Text
View/download PDF

31. The age of adult pilocytic astrocytoma cells

Author

Voronina, Natalia, Aichmüller, Christian, Kolb, Thorsten, Korshunov, Andrey, Ryzhova, Marina, Barnholtz-Sloan, Jill, Cioffi, Gino, Sill, Martin, von Deimling, Andreas, Pfister, Stefan M., Gronych, Jan, Jones, David T. W., Frisén, Jonas, Zapatka, Marc, and Ernst, Aurélie

Published
2021
Full Text
View/download PDF

32. Treatment response as surrogate to predict risk for disease progression in pediatric medulloblastoma with persistent magnetic resonance imaging lesions after first-line treatment.

Author

Obrecht-Sturm, Denise, Schömig, Lena, Mynarek, Martin, Bison, Brigitte, Schwarz, Rudolf, Pietsch, Torsten, Pfister, Stefan M, Sill, Martin, Sturm, Dominik, Sahm, Felix, Kortmann, Rolf-Dieter, Gerber, Nicolas U, Bueren, André O von, Fleischhack, Gudrun, Schüller, Ulrich, Nussbaumer, Gunther, Benesch, Martin, and Rutkowski, Stefan

Published
2024
Full Text
View/download PDF

33. Somatic gene delivery for flexible in vivo modeling of high-risk sarcoma

Author

Imle, Roland, primary, Blösel, Daniel, additional, Kommoss, Felix K.F., additional, Zhao, Eric Stutheit, additional, Autry, Robert, additional, Blume, Christina, additional, Lupar, Dmitry, additional, Schmitt, Lukas, additional, Winter, Claudia, additional, Wagner, Lena, additional, Placke, Sara, additional, von Eicke, Malte, additional, Hertwig, Michael, additional, Peterziel, Heike, additional, Oehme, Ina, additional, Scheuerman, Sophia, additional, Seitz, Christian, additional, Geyer, Florian H., additional, Cidre-Aranaz, Florencia, additional, Grünewald, Thomas G. P., additional, Vokuhl, Christian, additional, Chudasama, Priya, additional, Scholl, Claudia, additional, Schmidt, Claudia, additional, Günther, Patrick, additional, Sill, Martin, additional, Jones, Kevin B., additional, Pfister, Stefan M., additional, and Banito, Ana, additional

Published
2024
Full Text
View/download PDF

35. 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

36. 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
Full Text
View/download PDF

37. Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults

Author

Thomas, Christian, Wefers, Annika, Bens, Susanne, Nemes, Karolina, Agaimy, Abbas, Oyen, Florian, Vogelgesang, Silke, Rodriguez, Fausto J., Brett, Francesca M., McLendon, Roger, Bodi, Istvan, Burel-Vandenbos, Fanny, Keyvani, Kathy, Tippelt, Stefan, Poulsen, Frantz R., Lipp, Eric S., Giannini, Caterina, Reifenberger, Guido, Kuchelmeister, Klaus, Pietsch, Torsten, Kordes, Uwe, Siebert, Reiner, Frühwald, Michael C., Johann, Pascal D., Sill, Martin, Kool, Marcel, von Deimling, Andreas, Paulus, Werner, and Hasselblatt, Martin

Published
2020
Full Text
View/download PDF

39. YAP1-fusions in pediatric NF2-wildtype meningioma

Author

Sievers, Philipp, Chiang, Jason, Schrimpf, Daniel, Stichel, Damian, Paramasivam, Nagarajan, Sill, Martin, Gayden, Tenzin, Casalini, Belen, Reuss, David E., Dalton, James, Pajtler, Kristian W., Hänggi, Daniel, Herold-Mende, Christel, Rushing, Elisabeth, Korshunov, Andrey, Mawrin, Christian, Weller, Michael, Schlesner, Matthias, Wick, Wolfgang, Jabado, Nada, Jones, David T. W., Pfister, Stefan M., von Deimling, Andreas, Ellison, David W., and Sahm, Felix

Published
2020
Full Text
View/download PDF

40. 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

41. Sarcoma classification by DNA methylation profiling

Author

Koelsche, Christian, Schrimpf, Daniel, Stichel, Damian, Sill, Martin, Sahm, Felix, Reuss, David E., Blattner, Mirjam, Worst, Barbara, Heilig, Christoph E., Beck, Katja, Horak, Peter, Kreutzfeldt, Simon, Paff, Elke, Stark, Sebastian, Johann, Pascal, Selt, Florian, Ecker, Jonas, Sturm, Dominik, Pajtler, Kristian W., Reinhardt, Annekathrin, Wefers, Annika K., Sievers, Philipp, Ebrahimi, Azadeh, Suwala, Abigail, Fernández-Klett, Francisco, Casalini, Belén, Korshunov, Andrey, Hovestadt, Volker, Kommoss, Felix K. F., Kriegsmann, Mark, Schick, Matthias, Bewerunge-Hudler, Melanie, Milde, Till, Witt, Olaf, Kulozik, Andreas E., Kool, Marcel, Romero-Pérez, Laura, Grünewald, Thomas G. P., Kirchner, Thomas, Wick, Wolfgang, Platten, Michael, Unterberg, Andreas, Uhl, Matthias, Abdollahi, Amir, Debus, Jürgen, Lehner, Burkhard, Thomas, Christian, Hasselblatt, Martin, Paulus, Werner, Hartmann, Christian, Staszewski, Ori, Prinz, Marco, Hench, Jürgen, Frank, Stephan, Versleijen-Jonkers, Yvonne M. H., Weidema, Marije E., Mentzel, Thomas, Griewank, Klaus, de Álava, Enrique, Martín, Juan Díaz, Gastearena, Miguel A. Idoate, Chang, Kenneth Tou-En, Low, Sharon Yin Yee, Cuevas-Bourdier, Adrian, Mittelbronn, Michel, Mynarek, Martin, Rutkowski, Stefan, Schüller, Ulrich, Mautner, Viktor F., Schittenhelm, Jens, Serrano, Jonathan, Snuderl, Matija, Büttner, Reinhard, Klingebiel, Thomas, Buslei, Rolf, Gessler, Manfred, Wesseling, Pieter, Dinjens, Winand N. M., Brandner, Sebastian, Jaunmuktane, Zane, Lyskjær, Iben, Schirmacher, Peter, Stenzinger, Albrecht, Brors, Benedikt, Glimm, Hanno, Heining, Christoph, Tirado, Oscar M., Sáinz-Jaspeado, Miguel, Mora, Jaume, Alonso, Javier, del Muro, Xavier Garcia, Moran, Sebastian, Esteller, Manel, Benhamida, Jamal K., Ladanyi, Marc, Wardelmann, Eva, Antonescu, Cristina, Flanagan, Adrienne, Dirksen, Uta, Hohenberger, Peter, Baumhoer, Daniel, Hartmann, Wolfgang, Vokuhl, Christian, Flucke, Uta, Petersen, Iver, Mechtersheimer, Gunhild, Capper, David, Jones, David T. W., Fröhling, Stefan, Pfister, Stefan M., and von Deimling, Andreas

Published
2021
Full Text
View/download PDF

42. Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B

Author

Deng, Maximilian Y., Sturm, Dominik, Pfaff, Elke, Sill, Martin, Stichel, Damian, Balasubramanian, Gnana Prakash, Tippelt, Stephan, Kramm, Christof, Donson, Andrew M., Green, Adam L., Jones, Chris, Schittenhelm, Jens, Ebinger, Martin, Schuhmann, Martin U., Jones, Barbara C., van Tilburg, Cornelis M., Wittmann, Andrea, Golanov, Andrey, Ryzhova, Marina, Ecker, Jonas, Milde, Till, Witt, Olaf, Sahm, Felix, Reuss, David, Sumerauer, David, Zamecnik, Josef, Korshunov, Andrey, von Deimling, Andreas, Pfister, Stefan M., and Jones, David T. W.

Published
2021
Full Text
View/download PDF

44. PATH-64. COMPREHENSIVE CNS TUMOUR MOLECULAR DIAGNOSTICS USING THIRD GENERATION SEQUENCING

Author

Patel, Areeba, primary, Hinz, Felix, additional, Dogan, Helin, additional, Goebel, Kirsten, additional, Schrimpf, Daniel, additional, Goeller, Pauline, additional, Ritter, Michael, additional, Pfeifer, Lisa, additional, Blume, Christina, additional, Berghaus, Natalie, additional, Payne, Alexander, additional, Goidts, Violaine, additional, Loose, Matthew, additional, Unterberg, Andreas, additional, Wick, Wolfgang, additional, Pfister, Stefan, additional, Sill, Martin, additional, von Deimling, Andreas, additional, Jones, David, additional, Schlesner, Matthias, additional, and Sahm, Felix, additional

Published
2023
Full Text
View/download PDF

45. Author Correction: Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology

Author

Sturm, Dominik, primary, Capper, David, additional, Andreiuolo, Felipe, additional, Gessi, Marco, additional, Kölsche, Christian, additional, Reinhardt, Annekathrin, additional, Sievers, Philipp, additional, Wefers, Annika K., additional, Ebrahimi, Azadeh, additional, Suwala, Abigail K., additional, Gielen, Gerrit H., additional, Sill, Martin, additional, Schrimpf, Daniel, additional, Stichel, Damian, additional, Hovestadt, Volker, additional, Daenekas, Bjarne, additional, Rode, Agata, additional, Hamelmann, Stefan, additional, Previti, Christopher, additional, Jäger, Natalie, additional, Buchhalter, Ivo, additional, Blattner-Johnson, Mirjam, additional, Jones, Barbara C., additional, Warmuth-Metz, Monika, additional, Bison, Brigitte, additional, Grund, Kerstin, additional, Sutter, Christian, additional, Hirsch, Steffen, additional, Dikow, Nicola, additional, Hasselblatt, Martin, additional, Schüller, Ulrich, additional, Koch, Arend, additional, Gerber, Nicolas U., additional, White, Christine L., additional, Buntine, Molly K., additional, Kinross, Kathryn, additional, Algar, Elizabeth M., additional, Hansford, Jordan R., additional, Gottardo, Nicholas G., additional, Schuhmann, Martin U., additional, Thomale, Ulrich W., additional, Hernáiz Driever, Pablo, additional, Gnekow, Astrid, additional, Witt, Olaf, additional, Müller, Hermann L., additional, Calaminus, Gabriele, additional, Fleischhack, Gudrun, additional, Kordes, Uwe, additional, Mynarek, Martin, additional, Rutkowski, Stefan, additional, Frühwald, Michael C., additional, Kramm, Christof M., additional, von Deimling, Andreas, additional, Pietsch, Torsten, additional, Sahm, Felix, additional, Pfister, Stefan M., additional, and Jones, David. T. W., additional

Published
2023
Full Text
View/download PDF

46. The Site of Origin of Medulloblastoma: Surgical Observations Correlated to Molecular Groups

Author

Ciobanu-Caraus, Olga, primary, Czech, Thomas, additional, Peyrl, Andreas, additional, Haberler, Christine, additional, Kasprian, Gregor, additional, Furtner, Julia, additional, Kool, Marcel, additional, Sill, Martin, additional, Frischer, Josa M., additional, Cho, Anna, additional, Slavc, Irene, additional, Rössler, Karl, additional, Gojo, Johannes, additional, and Dorfer, Christian, additional

Published
2023
Full Text
View/download PDF

47. MYCN amplification drives an aggressive form of spinal ependymoma

Author

Ghasemi, David R., Sill, Martin, Okonechnikov, Konstantin, Korshunov, Andrey, Yip, Stephen, Schutz, Peter W., Scheie, David, Kruse, Anders, Harter, Patrick N., Kastelan, Marina, Wagner, Marlies, Hartmann, Christian, Benzel, Julia, Maass, Kendra K., Khasraw, Mustafa, Sträter, Ronald, Thomas, Christian, Paulus, Werner, Kratz, Christian P., Witt, Hendrik, Kawauchi, Daisuke, Herold-Mende, Christel, Sahm, Felix, Brandner, Sebastian, Kool, Marcel, Jones, David T. W., von Deimling, Andreas, Pfister, Stefan M., Reuss, David E., and Pajtler, Kristian W.

Published
2019
Full Text
View/download PDF

48. 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
Full Text
View/download PDF

49. Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes

Author

Sharma, Tanvi, Schwalbe, Edward C., Williamson, Daniel, Sill, Martin, Hovestadt, Volker, Mynarek, Martin, Rutkowski, Stefan, Robinson, Giles W., Gajjar, Amar, Cavalli, Florence, Ramaswamy, Vijay, Taylor, Michael D., Lindsey, Janet C., Hill, Rebecca M., Jäger, Natalie, Korshunov, Andrey, Hicks, Debbie, Bailey, Simon, Kool, Marcel, Chavez, Lukas, Northcott, Paul A., Pfister, Stefan M., and Clifford, Steven C.

Published
2019
Full Text
View/download PDF

50. Mapping pediatric brain tumors to their origins in the developing cerebellum

Author

Okonechnikov, Konstantin, primary, Joshi, Piyush, additional, Sepp, Mari, additional, Leiss, Kevin, additional, Sarropoulos, Ioannis, additional, Murat, Florent, additional, Sill, Martin, additional, Beck, Pengbo, additional, Chan, Kenneth Chun-Ho, additional, Korshunov, Andrey, additional, Sah, Felix, additional, Deng, Maximilian Y, additional, Sturm, Dominik, additional, DeSisto, John, additional, Donson, Andrew M, additional, Foreman, Nicholas K, additional, Green, Adam L, additional, Robinson, Giles, additional, Orr, Brent A, additional, Gao, Qingsong, additional, Darrow, Emily, additional, Hadley, Jennifer L, additional, Northcott, Paul A, additional, Gojo, Johannes, additional, Kawauchi, Daisuke, additional, Hovestadt, Volker, additional, Filbin, Mariella G, additional, von Deimling, Andreas, additional, Zuckermann, Marc, additional, Pajtler, Kristian W, additional, Kool, Marcel, additional, Jones, David T W, additional, Jäger, Natalie, additional, Kutscher, Lena M, additional, Kaessmann, Henrik, additional, and Pfister, Stefan M, additional

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results