2,125 results on '"Reifenberger, Guido"'
Search Results
2. A framework for standardised tissue sampling and processing during resection of diffuse intracranial glioma: joint recommendations from four RANO groups.
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Galldiks, Norbert, Kim, Michelle, Huse, Jason, Schnell, Oliver, Harter, Patrick, Mohme, Malte, von Baumgarten, Louisa, Albert, Nathalie, Huang, Raymond, Mehta, Minesh, van den Bent, Martin, Weller, Michael, Vogelbaum, Michael, Karschnia, Philipp, Smits, Marion, Reifenberger, Guido, Le Rhun, Emilie, Berger, Mitchel, Tonn, Joerg-Christian, Ellingson, Benjamin, and Chang, Susan
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Humans ,Brain Neoplasms ,Prospective Studies ,Biological Specimen Banks ,Neoplasm Recurrence ,Local ,Glioma - Abstract
Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.
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- 2023
3. mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism
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Levy, Tal, Voeltzke, Kai, Hruby, Laura, Alasad, Khawla, Bas, Zuelal, Snaebjörnsson, Marteinn, Marciano, Ran, Scharov, Katerina, Planque, Mélanie, Vriens, Kim, Christen, Stefan, Funk, Cornelius M., Hassiepen, Christina, Kahler, Alisa, Heider, Beate, Picard, Daniel, Lim, Jonathan K. M., Stefanski, Anja, Bendrin, Katja, Vargas-Toscano, Andres, Kahlert, Ulf D., Stühler, Kai, Remke, Marc, Elkabets, Moshe, Grünewald, Thomas G. P., Reichert, Andreas S., Fendt, Sarah-Maria, Schulze, Almut, Reifenberger, Guido, Rotblat, Barak, and Leprivier, Gabriel
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- 2024
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4. Improved prognostic stratification of patients with isocitrate dehydrogenase-mutant astrocytoma
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Weller, Michael, Felsberg, Jörg, Hentschel, Bettina, Gramatzki, Dorothee, Kubon, Nadezhda, Wolter, Marietta, Reusche, Matthias, Roth, Patrick, Krex, Dietmar, Herrlinger, Ulrich, Westphal, Manfred, Tonn, Joerg C., Regli, Luca, Maurage, Claude-Alain, von Deimling, Andreas, Pietsch, Torsten, Le Rhun, Emilie, and Reifenberger, Guido
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- 2024
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5. The long non-coding RNA OTX2-AS1 promotes tumor growth and predicts response to BCL-2 inhibition in medulloblastoma
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Qin, Nan, Paisana, Eunice, Picard, Daniel, Leprivier, Gabriel, Langini, Maike, Custódia, Carlos, Cascão, Rita, Conrad, Catleen, Peitzsch, Mirko, Stefanski, Anja, Stühler, Kai, Fischer, Ute, Faria, Claudia C., Dietrich, Sascha, Reifenberger, Guido, and Remke, Marc
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- 2023
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6. The oncological role of resection in newly diagnosed diffuse adult-type glioma defined by the WHO 2021 classification: a Review by the RANO resect group
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Karschnia, Philipp, Gerritsen, Jasper K W, Teske, Nico, Cahill, Daniel P, Jakola, Asgeir S, van den Bent, Martin, Weller, Michael, Schnell, Oliver, Vik-Mo, Einar O, Thon, Niklas, Vincent, Arnaud J P E, Kim, Michelle M, Reifenberger, Guido, Chang, Susan M, Hervey-Jumper, Shawn L, Berger, Mitchel S, and Tonn, Joerg-Christian
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- 2024
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7. Integrative multi-omics reveals two biologically distinct groups of pilocytic astrocytoma
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Picard, Daniel, Felsberg, Jörg, Langini, Maike, Stachura, Paweł, Qin, Nan, Macas, Jadranka, Reiss, Yvonne, Bartl, Jasmin, Selt, Florian, Sigaud, Romain, Meyer, Frauke-D., Stefanski, Anja, Stühler, Kai, Roque, Lucia, Roque, Rafael, Pandyra, Aleksandra A., Brozou, Triantafyllia, Knobbe-Thomsen, Christiane, Plate, Karl H., Roesch, Alexander, Milde, Till, Reifenberger, Guido, Leprivier, Gabriel, Faria, Claudia C., and Remke, Marc
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- 2023
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8. Long-term neurocognitive function and quality of life after multimodal therapy in adult glioma patients: a prospective long-term follow-up
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Pertz, Milena, Schlömer, Sabine, Seidel, Clemens, Hentschel, Bettina, Löffler, Markus, Schackert, Gabriele, Krex, Dietmar, Juratli, Tareq, Tonn, Joerg Christian, Schnell, Oliver, Vatter, Hartmut, Simon, Matthias, Westphal, Manfred, Martens, Tobias, Sabel, Michael, Bendszus, Martin, Dörner, Nils, Wick, Antje, Fliessbach, Klaus, Hoppe, Christian, Klingner, Marcel, Felsberg, Jörg, Reifenberger, Guido, Gramatzki, Dorothee, Weller, Michael, and Schlegel, Uwe
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- 2023
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9. Spatial immune profiling of glioblastoma identifies an inflammatory, perivascular phenotype associated with longer survival
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Wirsching, Hans-Georg, Felsberg, Jörg, Prummer, Michael, Moisoiu, Vlad, Lourman, Roxanne, Hertler, Caroline, Antonios, Michelle, Cimino, Patrick J., Roth, Patrick, Gorlia, Thierry, Prins, Robert M., Cloughesy, Timothy, Wen, Patrick Y., Holland, Eric C., Reifenberger, Guido, and Weller, Michael
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- 2023
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10. Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial
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Le Rhun, Emilie, Gorlia, Thierry, Felsberg, Jörg, Jongen, Joost, Maurage, Claude-Alain, Ducray, François, Gramatzki, Dorothee, Hau, Peter, Chinot, Olivier L., Preusser, Matthias, Cartalat, Stephanie, Roth, Patrick, van den Bent, Martin, Furtner, Julia, Collienne, Maike, Reifenberger, Guido, and Weller, Michael
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- 2024
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11. Sarcomatous Meningioma: Diagnostic Pitfalls and the Utility of Molecular Testing.
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Lucas, Calixto-Hope G, Devine, Patrick, Solomon, David A, Giannini, Caterina, Reifenberger, Guido, Dahiya, Sonika, Caccamo, Dario, and Perry, Arie
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Rare Diseases ,Brain Disorders ,Brain Cancer ,Cancer ,Adult ,Aged ,Biomarkers ,Tumor ,Diagnosis ,Differential ,Female ,Humans ,Meningeal Neoplasms ,Meningioma ,Neurofibromin 2 ,Sarcoma ,Anaplastic ,Molecular ,Neuropathology ,Sarcomatous ,Clinical Sciences ,Neurosciences ,Neurology & Neurosurgery - Abstract
Anaplastic meningiomas can have a sarcomatous appearance on histology but true sarcomatous (metaplastic) differentiation is rare. These tumors follow an aggressive clinical course with recurrence and poor clinical outcomes. Due to significant overlap in morphology and immunohistochemical profiles, distinguishing between sarcomatous transformation of a meningioma and a true sarcoma can be challenging. Here, we outline potential diagnostic pitfalls and the utility of ancillary molecular testing in 3 patients diagnosed with sarcomatous meningiomas. We report loss of typical meningothelial markers in sarcomatous meningiomas. Ancillary molecular testing can support the diagnosis of sarcomatous meningioma when a molecular signature consistent with meningioma is seen, such as inactivation of the NF2 gene. Recognition of this rare transformation in meningioma can prevent a misdiagnosis of a primary sarcoma, whether sporadic or radiation-induced from prior treatment of a more classic meningioma.
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- 2021
12. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary
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Louis, David N, Perry, Arie, Wesseling, Pieter, Brat, Daniel J, Cree, Ian A, Figarella-Branger, Dominique, Hawkins, Cynthia, Ng, HK, Pfister, Stefan M, Reifenberger, Guido, Soffietti, Riccardo, von Deimling, Andreas, and Ellison, David W
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Brain Disorders ,Cancer ,Brain Cancer ,Rare Diseases ,Neurosciences ,Brain ,Central Nervous System ,Central Nervous System Neoplasms ,Humans ,Pathology ,Molecular ,World Health Organization ,brian tumor ,central nervous system ,classification ,diagnosis ,brain tumor ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.
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- 2021
13. A framework for standardised tissue sampling and processing during resection of diffuse intracranial glioma: joint recommendations from four RANO groups
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Aldape, Kenneth, Baehring, Joachim M., Bello, Lorenzo, Brat, Daniel J., Cahill, Daniel P., Chung, Caroline, Colman, Howard, Dietrich, Jorg, Drummond, Katharine, Esquenazi, Yoshua, Gerstner, Elizabeth R., Furtner, Julia, Garibotto, Valentina, Kaufmann, Timothy J., Komori, Takashi, Kotecha, Rupesh, Liau, Linda M., Lupo, Janine M., Minniti, Giuseppe, Narita, Yoshitaka, Niyazi, Maximilian, Perry, Arie, Preusser, Matthias, Rudà, Roberta, Sanai, Nader, Schmidt, Nils-Ole, Steinbach, Joachim P., Thust, Stefanie C., Tolboom, Nelleke, van der Hoorn, Anouk, van der Vaart, Thijs, Verger, Antoine, Vik-Mo, Einar Osland, Watts, Colin, Westphal, Manfred, Wesseling, Pieter, Young, Jacob S., Karschnia, Philipp, Smits, Marion, Reifenberger, Guido, Le Rhun, Emilie, Ellingson, Benjamin M, Galldiks, Norbert, Kim, Michelle M, Huse, Jason T, Schnell, Oliver, Harter, Patrick N, Mohme, Malte, von Baumgarten, Louisa, Albert, Nathalie L, Huang, Raymond Y, Mehta, Minesh P, van den Bent, Martin, Weller, Michael, Vogelbaum, Michael A, Chang, Susan M, Berger, Mitchel S, and Tonn, Joerg-Christian
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- 2023
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14. Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1
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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
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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.
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- 2021
15. Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)
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Hertler, Caroline, Felsberg, Jörg, Gramatzki, Dorothee, Le Rhun, Emilie, Clarke, Jennifer, Soffietti, Riccardo, Wick, Wolfgang, Chinot, Olivier, Ducray, François, Roth, Patrick, McDonald, Kerrie, Hau, Peter, Hottinger, Andreas F., Reijneveld, Jaap, Schnell, Oliver, Marosi, Christine, Glantz, Michael, Darlix, Amélie, Lombardi, Giuseppe, Krex, Dietmar, Glas, Martin, Reardon, David A., van den Bent, Martin, Lefranc, Florence, Herrlinger, Ulrich, Razis, Evangelia, Carpentier, Antoine F., Phillips, Samuel, Rudà, Roberta, Wick, Antje, Tabouret, Emeline, Meyronet, David, Maurage, Claude-Alain, Rushing, Elisabeth, Rapkins, Robert, Bumes, Elisabeth, Hegi, Monika, Weyerbrock, Astrid, Aregawi, Dawit, Gonzalez-Gomez, Christian, Pellerino, Alessia, Klein, Martin, Preusser, Matthias, Bendszus, Martin, Golfinopoulos, Vassilis, von Deimling, Andreas, Gorlia, Thierry, Wen, Patrick Y., Reifenberger, Guido, and Weller, Michael
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- 2023
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16. A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR.
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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
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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.
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- 2021
17. cIMPACT‐NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT‐Utrecht meeting on future CNS tumor classification and grading
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Louis, David N, Wesseling, Pieter, Aldape, Kenneth, Brat, Daniel J, Capper, David, Cree, Ian A, Eberhart, Charles, Figarella‐Branger, Dominique, Fouladi, Maryam, Fuller, Gregory N, Giannini, Caterina, Haberler, Christine, Hawkins, Cynthia, Komori, Takashi, Kros, Johan M, Ng, HK, Orr, Brent A, Park, Sung‐Hye, Paulus, Werner, Perry, Arie, Pietsch, Torsten, Reifenberger, Guido, Rosenblum, Marc, Rous, Brian, Sahm, Felix, Sarkar, Chitra, Solomon, David A, Tabori, Uri, Bent, Martin J, Deimling, Andreas, Weller, Michael, White, Valerie A, and Ellison, David W
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Central Nervous System Neoplasms ,Humans ,Neoplasm Grading ,brain tumors ,central nervous system ,classification ,neoplasms ,Clinical Sciences ,Neurosciences ,Neurology & Neurosurgery ,Clinical sciences - Abstract
cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT-NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles-relating to classification categories, approaches to classification, nomenclature, and grading-that the group hopes will also inform the future classification of CNS neoplasms.
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- 2020
18. Longitudinal molecular trajectories of diffuse glioma in adults
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Barthel, Floris P, Johnson, Kevin C, Varn, Frederick S, Moskalik, Anzhela D, Tanner, Georgette, Kocakavuk, Emre, Anderson, Kevin J, Abiola, Olajide, Aldape, Kenneth, Alfaro, Kristin D, Alpar, Donat, Amin, Samirkumar B, Ashley, David M, Bandopadhayay, Pratiti, Barnholtz-Sloan, Jill S, Beroukhim, Rameen, Bock, Christoph, Brastianos, Priscilla K, Brat, Daniel J, Brodbelt, Andrew R, Bruns, Alexander F, Bulsara, Ketan R, Chakrabarty, Aruna, Chakravarti, Arnab, Chuang, Jeffrey H, Claus, Elizabeth B, Cochran, Elizabeth J, Connelly, Jennifer, Costello, Joseph F, Finocchiaro, Gaetano, Fletcher, Michael N, French, Pim J, Gan, Hui K, Gilbert, Mark R, Gould, Peter V, Grimmer, Matthew R, Iavarone, Antonio, Ismail, Azzam, Jenkinson, Michael D, Khasraw, Mustafa, Kim, Hoon, Kouwenhoven, Mathilde CM, LaViolette, Peter S, Li, Meihong, Lichter, Peter, Ligon, Keith L, Lowman, Allison K, Malta, Tathiane M, Mazor, Tali, McDonald, Kerrie L, Molinaro, Annette M, Nam, Do-Hyun, Nayyar, Naema, Ng, Ho Keung, Ngan, Chew Yee, Niclou, Simone P, Niers, Johanna M, Noushmehr, Houtan, Noorbakhsh, Javad, Ormond, D Ryan, Park, Chul-Kee, Poisson, Laila M, Rabadan, Raul, Radlwimmer, Bernhard, Rao, Ganesh, Reifenberger, Guido, Sa, Jason K, Schuster, Michael, Shaw, Brian L, Short, Susan C, Smitt, Peter A Sillevis, Sloan, Andrew E, Smits, Marion, Suzuki, Hiromichi, Tabatabai, Ghazaleh, Van Meir, Erwin G, Watts, Colin, Weller, Michael, Wesseling, Pieter, Westerman, Bart A, Widhalm, Georg, Woehrer, Adelheid, Yung, WK Alfred, Zadeh, Gelareh, Huse, Jason T, De Groot, John F, Stead, Lucy F, and Verhaak, Roel GW
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Neurosciences ,Brain Disorders ,Cancer ,Rare Diseases ,Brain Cancer ,Genetics ,Adult ,Chromosomes ,Human ,Pair 1 ,Chromosomes ,Human ,Pair 19 ,Disease Progression ,Glioma ,Humans ,Isocitrate Dehydrogenase ,Mutation ,Polymorphism ,Single Nucleotide ,Recurrence ,GLASS Consortium ,General Science & Technology - Abstract
The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.
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- 2019
19. Mid-term treatment-related cognitive sequelae in glioma patients
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Schlömer, Sabine, Felsberg, Jörg, Pertz, Milena, Hentschel, Bettina, Löffler, Markus, Schackert, Gabriele, Krex, Dietmar, Juratli, Tareq, Tonn, Joerg Christian, Schnell, Oliver, Vatter, Hartmut, Simon, Matthias, Westphal, Manfred, Martens, Tobias, Sabel, Michael, Bendszus, Martin, Dörner, Nils, Fliessbach, Klaus, Hoppe, Christian, Reifenberger, Guido, Weller, Michael, Schlegel, Uwe, and Network, for the German Glioma
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- 2022
- Full Text
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20. cIMPACT-NOW: a practical summary of diagnostic points from Round 1 updates.
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Louis, David N, Ellison, David W, Brat, Daniel J, Aldape, Kenneth, Capper, David, Hawkins, Cynthia, Paulus, Werner, Perry, Arie, Reifenberger, Guido, Figarella-Branger, Dominique, von Deimling, Andreas, and Wesseling, Pieter
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Humans ,Central Nervous System Neoplasms ,Brain Neoplasms ,Neuropathology ,Brain Cancer ,Brain Disorders ,Neurosciences ,Rare Diseases ,Cancer ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. From 2016 to 2019 (Round 1), cIMPACT published four updates. Update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed use of the additional term NEC (Not Elsewhere Classified). Update 2 issued clarifications regarding two diagnoses: Diffuse Midline Glioma, H3 K27M-mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH-mutant. Update 3 proposed molecular criteria that could be used in the setting of an IDH-wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma to infer that the tumor would behave similarly to a grade IV glioblastoma. Update 4 suggested that, in children and young adults, subtypes of IDH-wildtype/H3-wildtype diffuse gliomas may have distinct clinical features in the setting of a BRAFV600E mutation, FGFR1 alteration, other MAPK pathway alteration, or a MYB or MYBL1 rearrangement. The practical diagnostic relevance of these cIMPACT proposals is highlighted in this summary.
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- 2019
21. EGFR cooperates with EGFRvIII to recruit macrophages in glioblastoma
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An, Zhenyi, Knobbe-Thomsen, Christiane B, Wan, Xiaohua, Fan, Qi Wen, Reifenberger, Guido, and Weiss, William A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Rare Diseases ,Cancer ,Neurosciences ,Brain Disorders ,Animals ,Brain Neoplasms ,Cell Line ,Tumor ,Cell Movement ,Chemokine CCL2 ,Cytokines ,ErbB Receptors ,Female ,Gene Expression Regulation ,Neoplastic ,Glioblastoma ,Humans ,Macrophages ,Mice ,Microglia ,Neoplasm Transplantation ,Phosphorylation ,Proto-Oncogene Proteins p21(ras) ,RNA ,Small Interfering ,Signal Transduction ,Tumor Microenvironment ,Up-Regulation ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
: Amplification of the EGFR gene and its truncation mutant EGFRvIII are hallmarks of glioblastoma. Although coexpression of EGFR and EGFRvIII confers a growth advantage, how EGFR and EGFRvIII influence the tumor microenvironment remains incompletely understood. Here, we show that EGFR and EGFRvIII cooperate to induce macrophage infiltration via upregulation of the chemokine CCL2. EGFRvIII was significantly enriched in glioblastoma patient samples with high CCL2, and knockout of CCL2 in tumors coexpressing EGFR and EGFRvIII led to decreased infiltration of macrophages. KRAS was a critical signaling intermediate for EGFR- and EGFRvIII-induced expression of CCL2. Our results illustrate how EGFR and EGFRvIII direct the microenvironment in glioblastoma. SIGNIFICANCE: Full-length EGFR and truncated EGFRvIII work through KRAS to upregulate the chemokine CCL2 and drive macrophage infiltration in glioblastoma.
- Published
- 2018
22. Die WHO-Klassifikation der Tumoren des zentralen Nervensystems 2021: Neuerungen zur Diagnostik diffuser Gliome und deren Bedeutung für die klinische Praxis
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Weller, Michael, Knobbe-Thomsen, Christiane B., Le Rhun, Emilie, and Reifenberger, Guido
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- 2022
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23. The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors
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Bartl, Jasmin, Zanini, Marco, Bernardi, Flavia, Forget, Antoine, Blümel, Lena, Talbot, Julie, Picard, Daniel, Qin, Nan, Cancila, Gabriele, Gao, Qingsong, Nath, Soumav, Koumba, Idriss Mahoungou, Wolter, Marietta, Kuonen, François, Langini, Maike, Beez, Thomas, Munoz, Christopher, Pauck, David, Marquardt, Viktoria, Yu, Hua, Souphron, Judith, Korsch, Mascha, Mölders, Christina, Berger, Daniel, Göbbels, Sarah, Meyer, Frauke-Dorothee, Scheffler, Björn, Rotblat, Barak, Diederichs, Sven, Ramaswamy, Vijay, Suzuki, Hiromishi, Oro, Anthony, Stühler, Kai, Stefanski, Anja, Fischer, Ute, Leprivier, Gabriel, Willbold, Dieter, Steger, Gerhard, Buell, Alexander, Kool, Marcel, Lichter, Peter, Pfister, Stefan M., Northcott, Paul A., Taylor, Michael D., Borkhardt, Arndt, Reifenberger, Guido, Ayrault, Olivier, and Remke, Marc
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- 2022
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24. Droplet digital PCR-based analyses for robust, rapid, and sensitive molecular diagnostics of gliomas
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Wolter, Marietta, Felsberg, Jörg, Malzkorn, Bastian, Kaulich, Kerstin, and Reifenberger, Guido
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- 2022
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25. AMPLIFY-NEOVAC: a randomized, 3-arm multicenter phase I trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with an immune checkpoint inhibitor targeting programmed death-ligand 1 in isocitrate dehydrogenase 1 mutant gliomas
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Bunse, Lukas, Rupp, Anne-Kathleen, Poschke, Isabel, Bunse, Theresa, Lindner, Katharina, Wick, Antje, Blobner, Jens, Misch, Martin, Tabatabai, Ghazaleh, Glas, Martin, Schnell, Oliver, Gempt, Jens, Denk, Monika, Reifenberger, Guido, Bendszus, Martin, Wuchter, Patrick, Steinbach, Joachim P, Wick, Wolfgang, and Platten, Michael
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- 2022
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26. EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma
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Voeltzke, Kai, Scharov, Katerina, Funk, Cornelius Maximilian, Kahler, Alisa, Picard, Daniel, Hauffe, Laura, Orth, Martin F., Remke, Marc, Esposito, Irene, Kirchner, Thomas, Schramm, Alexander, Rotblat, Barak, Grünewald, Thomas G. P., Reifenberger, Guido, and Leprivier, Gabriel
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- 2022
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27. Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) expression in glioblastoma is driven by ETS1- and MYBL2-dependent transcriptional activation
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Hauffe, Laura, Picard, Daniel, Musa, Julian, Remke, Marc, Grünewald, Thomas G. P., Rotblat, Barak, Reifenberger, Guido, and Leprivier, Gabriel
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- 2022
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28. Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival
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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
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- 2022
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29. GOPC:ROS1 and other ROS1 fusions represent a rare but recurrent drug target in a variety of glioma types
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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
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- 2021
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30. Glioma through the looking GLASS: molecular evolution of diffuse gliomas and the Glioma Longitudinal Analysis Consortium
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Aldape, Kenneth, Amin, Samirkumar B, Ashley, David M, Barnholtz-Sloan, Jill S, Bates, Amanda J, Beroukhim, Rameen, Bock, Christoph, Brat, Daniel J, Claus, Elizabeth B, Costello, Joseph F, de Groot, John F, Finocchiaro, Gaetano, French, Pim J, Gan, Hui K, Griffith, Brent, Herold-Mende, Christel C, Horbinski, Craig, Iavarone, Antonio, Kalkanis, Steven N, Karabatsou, Konstantina, Kim, Hoon, Kouwenhoven, Mathilde CM, McDonald, Kerrie L, Miletic, Hrvoje, Nam, Do-Hyun, Ng, Ho Keung, Niclou, Simone P, Noushmehr, Houtan, Ormond, D Ryan, Poisson, Laila M, Reifenberger, Guido, Roncaroli, Federico, Sa, Jason K, Smitt, Peter AE Sillevis, Smits, Marion, Souza, Camila F, Tabatabai, Ghazaleh, Van Meir, Erwin G, Verhaak, Roel GW, Watts, Colin, Wesseling, Pieter, Woehrer, Adelheid, Yung, WK Alfred, Jungk, Christine, Hau, Ann-Christin, van Dyck, Eric, Westerman, Bart A, Yin, Julia, Abiola, Olajide, Zeps, Nikolaj, Grimmond, Sean, Buckland, Michael, Khasraw, Mustafa, Sulman, Erik P, Muscat, Andrea M, and Stead, Lucy
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Cancer ,Human Genome ,Brain Cancer ,Rare Diseases ,Orphan Drug ,Brain Disorders ,Neurosciences ,Genetics ,Brain Neoplasms ,Evolution ,Molecular ,Genomics ,Glioma ,Humans ,Longitudinal Studies ,characterization ,evolution ,glioma ,sequencing ,subtypes ,GLASS Consortium ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal Analysis Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities and, ultimately, improved outcomes for a patient population in need.
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- 2018
31. ACTR-23. MOLECULAR GENETIC, HOST-DERIVED AND CLINICAL DETERMINANTS OF LONG-TERM SURVIVAL IN GLIOBLASTOMA: FIRST RESULTS FROM THE BRAIN TUMOR FUNDERS’ COLLABORATIVE CONSORTIUM
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Happold, Caroline, Felsberg, Jörg, Clarke, Jennifer, Soffietti, Riccardo, Marosi, Christine, Krex, Dietmar, Ducray, François, Hau, Peter, Reijneveld, Jaap, Weyerbrock, Astrid, Wick, Antje, Reardon, David, Glas, Martin, Razis, Evangelia, Herrlinger, Ulrich, Tonn, Joerg-Christian, Carpentier, Antoine F, Lefranc, Florence, Rhun, Emilie Le, Verschuere, Tina, Golfinopoulos, Vassilis, Klein, Martin, Reifenberger, Guido, and Weller, Michael
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Neurosciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Abstract BACKGROUND Survival in glioblastoma patients is usually in the range of 12–15 months, and less than 5% of patients survive 5 years from diagnosis. Little is known about factors influencing long-term survival. METHODS A consortium generously funded by the Brain Tumor Funders’ Collaborative comprising more than 20 clinical sites in Europe, the US, and Australia registers patients with glioblastoma who survived for at least 5 years. The aim of the study is a better understanding of factors contributing to prolonged survival by assessment of (i) clinical features, (ii) molecular parameters, (iii) therapy and quality of life-related factors, and (iv) immunological parameters. The histopathological diagnosis of glioblastoma is centrally reviewed at study entry. Clinical characteristics including imaging data are collected at the European Organisation for Research and Treatment of Cancer (EORTC) in Brussels, Belgium. Comprehensive molecular analyses are performed at the German Cancer Research Center (DKFZ), Germany. Immunological parameters are analyzed in Zurich, Switzerland. Alive patients are followed by neurocognitive assessments additionally. RESULTS At the cut-off of May 30, 2017, 182 patients have been registered by 17 sites; 107 patients are alive, more than half of which contribute to the neurocognitive assessments and patient-related outcome studies, as well as the immunological studies. First comprehensive results of disease characteristics with a cut-off of September 30, 2017, will be presented. CONCLUSIONS The collaborative effort of this consortium by comprehensive characterization of molecular parameters, immunological aspects, and individual clinical and therapy-related determinants will contribute to a better understanding of factors that modulate the course of this disease.
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- 2017
32. Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors
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Blümel, Lena, Qin, Nan, Berlandi, Johannes, Paisana, Eunice, Cascão, Rita, Custódia, Carlos, Pauck, David, Picard, Daniel, Langini, Maike, Stühler, Kai, Meyer, Frauke-Dorothee, Göbbels, Sarah, Malzkorn, Bastian, Liebau, Max C., Barata, João T., Jeibmann, Astrid, Kerl, Kornelius, Erkek, Serap, Kool, Marcel, Pfister, Stefan M., Johann, Pascal D., Frühwald, Michael C., Borkhardt, Arndt, Reifenberger, Guido, Faria, Claudia C., Fischer, Ute, Hasselblatt, Martin, Bartl, Jasmin, and Remke, Marc
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- 2022
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33. Corrigendum to “Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial” [Eur J Cancer 198 (2024) 113475]
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Le Rhun, Emilie, primary, Gorlia, Thierry, additional, Felsberg, Jörg, additional, Jongen, Joost, additional, Maurage, Claude-Alain, additional, Ducray, François, additional, Gramatzki, Dorothee, additional, Hau, Peter, additional, Chinot, Olivier L., additional, Preusser, Matthias, additional, Cartalat, Stephanie, additional, Roth, Patrick, additional, van den Bent, Martin, additional, Furtner, Julia, additional, Collienne, Maike, additional, Reifenberger, Guido, additional, and Weller, Michael, additional
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- 2024
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34. TheEIF4EBP1gene encoding 4EBP1 is transcriptionally upregulated by MYC and linked to shorter survival in medulloblastoma
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Hruby, Laura, primary, Scharov, Katerina, additional, Delaidelli, Alberto, additional, Picard, Daniel, additional, Dunham, Christopher, additional, Lewandowska, Oksana, additional, Reiff, Tobias, additional, Larcher, Magalie, additional, Pouponnot, Celio, additional, Sorensen, Poul HB, additional, Rotblat, Barak, additional, Reifenberger, Guido, additional, Remke, Marc, additional, and Leprivier, Gabriel, additional
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- 2024
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35. Table S1 from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen
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Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary
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36. Supp Figures from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen
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Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary
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37. Supplemental Figures Legends from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen
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Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary
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38. Data from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen
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Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary
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39. Supplementary Appendix from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen
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Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary
- Published
- 2024
- Full Text
- View/download PDF
40. Circular RNA profiling distinguishes medulloblastoma groups and shows aberrant RMST overexpression in WNT medulloblastoma
- Author
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Rickert, Daniel, Bartl, Jasmin, Picard, Daniel, Bernardi, Flavia, Qin, Nan, Lovino, Marta, Puget, Stéphanie, Meyer, Frauke-Dorothee, Mahoungou Koumba, Idriss, Beez, Thomas, Varlet, Pascale, Dufour, Christelle, Fischer, Ute, Borkhardt, Arndt, Reifenberger, Guido, Ayrault, Olivier, and Remke, Marc
- Published
- 2021
- Full Text
- View/download PDF
41. Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma:The EORTC 1608 STEAM trial
- Author
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Le Rhun, Emilie, Gorlia, Thierry, Felsberg, Jörg, Jongen, Joost, Maurage, Claude Alain, Ducray, François, Gramatzki, Dorothee, Hau, Peter, Chinot, Olivier L., Preusser, Matthias, Cartalat, Stephanie, Roth, Patrick, van den Bent, Martin, Furtner, Julia, Collienne, Maike, Reifenberger, Guido, Weller, Michael, Le Rhun, Emilie, Gorlia, Thierry, Felsberg, Jörg, Jongen, Joost, Maurage, Claude Alain, Ducray, François, Gramatzki, Dorothee, Hau, Peter, Chinot, Olivier L., Preusser, Matthias, Cartalat, Stephanie, Roth, Patrick, van den Bent, Martin, Furtner, Julia, Collienne, Maike, Reifenberger, Guido, and Weller, Michael
- Abstract
Background: Zotiraciclib (TG02) is an oral multi-cyclin dependent kinase (CDK) inhibitor thought to inhibit tumor growth via CDK-9-dependent depletion of survival proteins such as c-MYC and MCL-1 which are frequently overexpressed in glioblastoma. Methods: EORTC 1608 (NCT03224104) (STEAM) had a three parallel group (A,B,C) phase Ib, open-label, non-randomized, multicenter design in IDH wild-type newly diagnosed glioblastoma or anaplastic astrocytoma. Groups A and B explored the maximum tolerated dose (MTD) of TG02 in elderly patients, in combination with hypofractionated radiotherapy alone (group A) or temozolomide alone (group B), according to O6-methylguanine DNA methyltransferase promoter methylation status determined centrally. Group C explored single agent activity of TG02 at first relapse after temozolomide chemoradiotherapy with a primary endpoint of progression-free survival at 6 months (PFS-6). Tumor expression of CDK-9, c-MYC and MCL-1 was determined by immunohistochemistry.Results: The MTD was 150 mg twice weekly in combination with radiotherapy alone (group A) or temozolomide alone (group B). Two dose-limiting toxicities were observed at 150 mg: one in group A (grade 3 seizure), one in group B (multiple grade 1 events). Main toxicities included neutropenia, gastrointestinal disorders and hepatotoxicity. PFS-6 in group C was 6.7%. CDK-9, c-MYC and MCL-1 were confirmed to be expressed and their expression was moderately cross-correlated. High protein levels of MCL-1 were associated with inferior survival. Conclusions: TG02 exhibits overlapping toxicity with alkylating agents and low single agent clinical activity in recurrent glioblastoma. The role of CDK-9 and its down-stream effectors as prognostic factors and therapeutic targets in glioblastoma warrants further study.
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- 2024
42. The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen
- Author
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Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, et al, Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, and et al
- Abstract
Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histological progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution towards an IDHwt-like phenotype.
- Published
- 2024
43. Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial
- Author
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Le Rhun, Emilie; https://orcid.org/0000-0002-9408-3278, Gorlia, Thierry, Felsberg, Jörg; https://orcid.org/0000-0001-9652-1799, Jongen, Joost, Maurage, Claude-Alain, Ducray, François, Gramatzki, Dorothee; https://orcid.org/0000-0002-9054-5498, Hau, Peter; https://orcid.org/0000-0003-3894-5053, Chinot, Olivier L; https://orcid.org/0000-0001-6317-9691, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Cartalat, Stéphanie, Roth, Patrick; https://orcid.org/0000-0003-3897-214X, van den Bent, Martin; https://orcid.org/0000-0001-5710-5127, Furtner, Julia, Collienne, Maike, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Le Rhun, Emilie; https://orcid.org/0000-0002-9408-3278, Gorlia, Thierry, Felsberg, Jörg; https://orcid.org/0000-0001-9652-1799, Jongen, Joost, Maurage, Claude-Alain, Ducray, François, Gramatzki, Dorothee; https://orcid.org/0000-0002-9054-5498, Hau, Peter; https://orcid.org/0000-0003-3894-5053, Chinot, Olivier L; https://orcid.org/0000-0001-6317-9691, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Cartalat, Stéphanie, Roth, Patrick; https://orcid.org/0000-0003-3897-214X, van den Bent, Martin; https://orcid.org/0000-0001-5710-5127, Furtner, Julia, Collienne, Maike, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, and Weller, Michael; https://orcid.org/0000-0002-1748-174X
- Abstract
BACKGROUND Zotiraciclib (TG02) is an oral multi-cyclin dependent kinase (CDK) inhibitor thought to inhibit tumor growth via CDK-9-dependent depletion of survival proteins such as c-MYC and MCL-1 which are frequently overexpressed in glioblastoma. METHODS EORTC 1608 (NCT03224104) (STEAM) had a three parallel group (A,B,C) phase Ib, open-label, non-randomized, multicenter design in IDH wild-type newly diagnosed glioblastoma or anaplastic astrocytoma. Groups A and B explored the maximum tolerated dose (MTD) of TG02 in elderly patients, in combination with hypofractionated radiotherapy alone (group A) or temozolomide alone (group B), according to O$^{6}$-methylguanine DNA methyltransferase promoter methylation status determined centrally. Group C explored single agent activity of TG02 at first relapse after temozolomide chemoradiotherapy with a primary endpoint of progression-free survival at 6 months (PFS-6). Tumor expression of CDK-9, c-MYC and MCL-1 was determined by immunohistochemistry. RESULTS The MTD was 150 mg twice weekly in combination with radiotherapy alone (group A) or temozolomide alone (group B). Two dose-limiting toxicities were observed at 150 mg: one in group A (grade 3 seizure), one in group B (multiple grade 1 events). Main toxicities included neutropenia, gastrointestinal disorders and hepatotoxicity. PFS-6 in group C was 6.7%. CDK-9, c-MYC and MCL-1 were confirmed to be expressed and their expression was moderately cross-correlated. High protein levels of MCL-1 were associated with inferior survival. CONCLUSIONS TG02 exhibits overlapping toxicity with alkylating agents and low single agent clinical activity in recurrent glioblastoma. The role of CDK-9 and its down-stream effectors as prognostic factors and therapeutic targets in glioblastoma warrants further study.
- Published
- 2024
44. The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen
- Author
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Malta, Tathiane M., Sabedot, Thais S., Morosini, Natalia S., Datta, Indrani, Garofano, Luciano, Vallentgoed, Wies, Varn, Frederick S., Aldape, Kenneth, D'Angelo, Fulvio, Bakas, Spyridon, Barnholtz-Sloan, Jill S., Gan, Hui K., Hasanain, Mohammad, Hau, Ann Christin, Johnson, Kevin C., Cazacu, Simona, deCarvalho, Ana C., Khasraw, Mustafa, Kocakavuk, Emre, Kouwenhoven, Mathilde C.M., Migliozzi, Simona, Niclou, Simone P., Niers, Johanna M., Ormond, D. Ryan, Paek, Sun Ha, Reifenberger, Guido, Smitt, Peter A.Sillevis, Smits, Marion, Stead, Lucy F., van den Bent, Martin J., Van Meir, Erwin G., Walenkamp, Annemiek, Weiss, Tobias, Weller, Michael, Westerman, Bart A., Ylstra, Bauke, Wesseling, Pieter, Lasorella, Anna, French, Pim J., Poisson, Laila M., Verhaak, Roel G.W., Iavarone, Antonio, Noushmehr, Houtan, Malta, Tathiane M., Sabedot, Thais S., Morosini, Natalia S., Datta, Indrani, Garofano, Luciano, Vallentgoed, Wies, Varn, Frederick S., Aldape, Kenneth, D'Angelo, Fulvio, Bakas, Spyridon, Barnholtz-Sloan, Jill S., Gan, Hui K., Hasanain, Mohammad, Hau, Ann Christin, Johnson, Kevin C., Cazacu, Simona, deCarvalho, Ana C., Khasraw, Mustafa, Kocakavuk, Emre, Kouwenhoven, Mathilde C.M., Migliozzi, Simona, Niclou, Simone P., Niers, Johanna M., Ormond, D. Ryan, Paek, Sun Ha, Reifenberger, Guido, Smitt, Peter A.Sillevis, Smits, Marion, Stead, Lucy F., van den Bent, Martin J., Van Meir, Erwin G., Walenkamp, Annemiek, Weiss, Tobias, Weller, Michael, Westerman, Bart A., Ylstra, Bauke, Wesseling, Pieter, Lasorella, Anna, French, Pim J., Poisson, Laila M., Verhaak, Roel G.W., Iavarone, Antonio, and Noushmehr, Houtan
- Abstract
Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histologic progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neoangiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution toward an IDHwt-like phenotype.
- Published
- 2024
45. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood
- Author
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Weller, Michael, van den Bent, Martin, Preusser, Matthias, Le Rhun, Emilie, Tonn, Jörg C., Minniti, Giuseppe, Bendszus, Martin, Balana, Carmen, Chinot, Olivier, Dirven, Linda, French, Pim, Hegi, Monika E., Jakola, Asgeir S., Platten, Michael, Roth, Patrick, Rudà, Roberta, Short, Susan, Smits, Marion, Taphoorn, Martin J. B., von Deimling, Andreas, Westphal, Manfred, Soffietti, Riccardo, Reifenberger, Guido, and Wick, Wolfgang
- Published
- 2021
- Full Text
- View/download PDF
46. Pathology and Classification of Tumors of the Central Nervous System
- Author
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Reifenberger, Guido, Blümcke, Ingmar, Wesseling, Pieter, Pietsch, Torsten, Paulus, Werner, Tonn, Jörg-Christian, editor, Reardon, David A., editor, Rutka, James T., editor, and Westphal, Manfred, editor
- Published
- 2019
- Full Text
- View/download PDF
47. Epigenetic modification and characterization of the MGMT promoter region using CRISPRoff in glioblastoma cells
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Weber, Remi, primary, Weller, Michael, additional, Reifenberger, Guido, additional, and Vasella, Flavio, additional
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- 2024
- Full Text
- View/download PDF
48. Direct excitatory synapses between neurons and tumor cells drive brain metastatic seeding of breast cancer and melanoma
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Venkataramani, Varun, primary, Karreman, Matthia Andrea, additional, Nguyen, Linh Cathrin, additional, Tehranian, Cedric, additional, Hebach, Nils, additional, Mayer, Chante, additional, Meyer, Lasse, additional, Mughal, Sadaf, additional, Reifenberger, Guido, additional, Felsberg, Joerg, additional, Koehrer, Karl, additional, Schubert, Marc Cicero, additional, Westphal, Dana, additional, Breckwolt, Michael, additional, Brors, Benedikt, additional, Wick, Wolfgang, additional, Kuner, Thomas, additional, and Winkler, Frank, additional
- Published
- 2024
- Full Text
- View/download PDF
49. Age-stratified clinical performance and survival of patients with IDH-wildtype glioblastoma homogeneously treated by radiotherapy with concomitant and maintenance temozolomide
- Author
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Berger, Kerstin, Turowski, Bernd, Felsberg, Jörg, Malzkorn, Bastian, Reifenberger, Guido, Steiger, Hans-Jakob, Budach, Wilfried, Haussmann, Jan, Knipps, Johannes, Rapp, Marion, Hänggi, Daniel, Sabel, Michael, Mijderwijk, Hendrik-Jan, and Kamp, Marcel A.
- Published
- 2021
- Full Text
- View/download PDF
50. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.
- Author
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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
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