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53. A Territory-wide Study Investigating the Dose and Efficacy of Different Bacillus Calmette-Guérin Strains in Patients with Intermediate- and High-risk Non–muscle-invasive Bladder Cancer

Author

Liu, Kang, Zhao, Hongda, Chen, Xuan, Nicoletti, Rossella, Vasdev, Nikhil, Chiu, Peter Ka-Fung, Ng, Chi-Fai, Kawada, Tatsushi, Laukhtina, Ekaterina, Mori, Keiichiro, Yanagisawa, Takafumi, D'Andrea, David, von Deimling, Markus, Albisinni, Simone, Krajewski, Wojciech, Pradere, Benjamin, Soria, Francesco, Moschini, Marco, Enikeev, Dmitry, Shariat, Shahrokh, Kamat, Ashish, Giannarini, Gianluca, and Teoh, Jeremy Yuen-Chun

Published
2024
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55. Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

Author

del Olmo, Ricardo, Anderson, Gary, Reddel, Helen, Rabahi, Marcelo, McIvor, Andrew, Sadatsafavi, Mohsen, Weinreich, Ulla, Burgel, Pierre-Régis, Devouassoux, Gilles, Papi, Alberto, Inoue, Hiromasa, Rendon, Adrián, van den Berge, Maarten, Beasley, Richard, García-Navarro, Alvar Agusti, Faner, Rosa, Rivera, José Olaguibel, Janson, Christer, Bilińska-Izydorczyk, Magdalena, Fagerås, Malin, Fihn-Wikander, Titti, Franzén, Stefan, Keen, Christina, Ostridge, Kristoffer, Chalmers, James, Harrison, Timothy, Pavord, Ian, Price, David, Azim, Adnan, Belton, Laura, Blé, Francois-Xavier, Erhard, Clement, Gairy, Kerry, Hughes, Rod, Lassi, Glenda, Müllerová, Hana, Rapsomaniki, Eleni, Scott, Ian Christopher, Chipps, Bradley, Christenson, Stephanie, Make, Barry, Tomaszewski, Erin, Benhabib, Gabriel, Ruiz, Xavier Bocca, Lisanti, Raul Eduardo, Marino, Gustavo, Mattarucco, Walter, Nogueira, Juan, Parody, Maria, Pascale, Pablo, Rodriguez, Pablo, Silva, Damian, Svetliza, Graciela, Victorio, Carlos F., Rolon, Roxana Willigs, Yañez, Anahi, Baines, Stuart, Bowler, Simon, Bremner, Peter, Bull, Sheetal, Carroll, Patrick, Chaalan, Mariam, Farah, Claude, Hammerschlag, Gary, Hancock, Kerry, Harrington, Zinta, Katsoulotos, Gregory, Kim, Joshua, Langton, David, Lee, Donald, Peters, Matthew, Prassad, Lakshman, Sajkov, Dimitar, Santiago, Francis, Simpson, Frederick Graham, Tai, Sze, Thomas, Paul, Wark, Peter, Delfini Cançado, José Eduardo, Cunha, Thúlio, Lima, Marina, Cardoso, Alexandre Pinto, FitzGerald, J. Mark, Anees, Syed, Bertley, John, Bell, Alan, Cheema, Amarjit, Chouinard, Guy, Csanadi, Michael, Dhar, Anil, Dhillon, Ripple, Kanawaty, David, Kelly, Allan, Killorn, William, Landry, Daniel, Luton, Robert, Mandhane, Piushkumar, Pek, Bonavuth, Petrella, Robert, Stollery, Daniel, Wang, Chen, Chen, Meihua, Chen, Yan, Gu, Wei, Christopher Hui, Kim Ming, Li, Manxiang, Li, Shiyue, Lijun, Ma, Qin, Guangyue, Song, Weidong, Tan, Wei, Tang, Yijun, Wang, Tan, Wen, Fuqiang, Wu, Feng, Xiang, PingChao, Xiao, Zuke, Xiong, Shengdao, Yang, Jinghua, Yang, Jingping, Zhang, Caiqing, Zhang, Min, Zhang, Ping, Zhang, Wei, Zheng, Xiaohe, Zhu, Dan, Bueno, Carlos Matiz, Grimaldos, Fabio Bolivar, Arboleda, Alejandra Cañas, Molina de Salazar, Dora, Bendstrup, Elisabeth, Hilberg, Ole, Kjellerup, Carsten, Raherison, Chantal, Bonniaud, Philippe, Brun, Olivier, Chouaid, Christos, Couturaud, Francis, de Blic, Jacques, Debieuvre, Didier, Delsart, Dominique, Demaegdt, Axelle, Demoly, Pascal, Deschildre, Antoine, Egron, Carole, Falchero, Lionel, Goupil, François, Kessler, Romain, Le Roux, Pascal, Mabire, Pascal, Mahay, Guillaume, Martinez, Stéphanie, Melloni, Boris, Moreau, Laurent, Riviere, Emilie, Roux-Claudé, Pauline, Soulier, Michel, Vignal, Guillaume, Yaici, Azzedine, Bals, Robert, Aries, Sven Philip, Beck, Ekkehard, Deimling, Andreas, Feimer, Jan, Grimm-Sachs, Vera, Groth, Gesine, Herth, Felix, Hoheisel, Gerhard, Kanniess, Frank, Lienert, Thomas, Mronga, Silke, Reinhardt, Jörg, Schlenska, Christian, Stolpe, Christoph, Teber, Ishak, Timmermann, Hartmut, Ulrich, Thomas, Velling, Peter, Wehgartner-Winkler, Sabina, Welling, Juergen, Winkelmann, Ernst-Joachim, Barbetta, Carlo, Braido, Fulvio, Cardaci, Vittorio, Clini, Enrico Maria, Costantino, Maria Teresa, Cuttitta, Giuseppina, di Gioacchino, Mario, Fois, Alessandro, Foschino-Barbaro, Maria Pia, Gammeri, Enrico, Inchingolo, Riccardo, Lavorini, Federico, Molino, Antonio, Nucera, Eleonora, Patella, Vincenzo, Pesci, Alberto, Ricciardolo, Fabio, Rogliani, Paola, Sarzani, Riccardo, Vancheri, Carlo, Vincenti, Rigoletta, Endo, Takeo, Fujita, Masaki, Hara, Yu, Horiguchi, Takahiko, Hosoi, Keita, Ide, Yumiko, Inomata, Minehiko, Inoue, Koji, Inoue, Sumito, Kato, Motokazu, Kawasaki, Masayuki, Kawayama, Tomotaka, Kita, Toshiyuki, Kobayashi, Kanako, Koto, Hiroshi, Nishi, Koichi, Saito, Junpei, Shimizu, Yasuo, Shirai, Toshihiro, Sugihara, Naruhiko, Takahashi, Ken-ichi, Tashimo, Hiroyuki, Tomii, Keisuke, Yamada, Takashi, Yanai, Masaru, Rendon, Adrian, Javier, Ruth Cerino, Peregrina, Alfredo Domínguez, Corzo, Marco Fernández, Gonzalez, Efraín Montano, Ramírez-Venegas, Alejandra, Boersma, Willem, Djamin, R.S., Eijsvogel, Michiel, Franssen, Frits, Goosens, Martijn, Graat-Verboom, Lidwien, Veen, Johannes in 't, Janssen, Rob, Kuppens, Kim, van de Ven, Mario, Bakke, Per, Brunstad, Ole Petter, Einvik, Gunnar, Høines, Kristian Jong, Khusrawi, Alamdar, Oien, Torbjorn, Yoon, Ho Joo, Chang, Yoon-Seok, Cho, Young Joo, Hwang, Yong Il, Kim, Woo Jin, Koh, Young-Il, Lee, Byung-Jae, Lee, Kwan-Ho, Lee, Sang-Pyo, Lee, Yong Chul, Lim, Seong Yong, Min, Kyung Hun, Oh, Yeon-Mok, Park, Choon-Sik, Park, Hae-Sim, Park, Heung-Woo, Rhee, Chin Kook, Yoon, Hyoung-Kyu, Andújar, Rubén, Anoro, Laura, García, María Buendía, Mozo, Paloma Campo, Campos, Sergio, Maldonado, Francisco Casas, Martínez, Manuel Castilla, Serrano, Carolina Cisneros, Casanova, Lorena Comeche, Corbacho, Dolores, Del Campo Matías, Felix, Echave-Sustaeta, Jose, Corral, Gloria Francisco, Setién, Pedro Gamboa, Clemente, Marta García, Núñez, Ignacio García, Robaina, Jose García, Salmones, Mercedes García, Marín Trigo, Jose Maria, Fernandez, Marta Nuñez, Palomo, Sara Nuñez, Pérez de Llano, Luis, Bastida, Ana Pueyo, Rañó, Ana, González-Moro, José Rodríguez, Reig, Albert Roger, Garrido, José Velasco, Curiac, Dan, Lif-Tiberg, Cornelia, Luts, Anders, Råhlen, Lennart, Rustscheff, Stefan, Adams, Frances, Bradman, Drew, Broughton, Emma, Cosgrove, John, Flood-Page, Patrick, Fuller, Elizabeth, Hartley, David, Hattotuwa, Keith, Jones, Gareth, Lewis, Keir, McGarvey, Lorcan, Morice, Alyn, Pandya, Preeti, Patel, Manish, Roy, Kay, Sathyamurthy, Ramamurthy, Thiagarajan, Swaminathan, Turner, Alice, Vestbo, Jorgen, Wedzicha, Wisia, Wilkinson, Tom, Wilson, Pete, Al-Asadi, Lo’Ay, Anholm, James, Averill, Francis, Bansal, Sandeep, Baptist, Alan, Campbell, Colin, Campos, Michael A., Crook, Gretchen, DeLeon, Samuel, Eid, Alain, Epstein, Ellen, Fritz, Stephen, Harris, Hoadley, Hewitt, Mitzie, Holguin, Fernando, Hudes, Golda, Jackson, Richard, Kaufman, Alan, Kaufman, David, Klapholz, Ari, Krishna, Harshavardhan, Lee, Daria, Lin, Robert, Maselli-Caceres, Diego, Mehta, Vinay, Moy, James N., Nwokoro, Ugo, Parikh, Purvi, Parikh, Sudhir, Perrino, Frank, Ruhlmann, James, Sassoon, Catherine, Settipane, Russell A., Sousa, Daniel, Sriram, Peruvemba, Wachs, Richard, Ding, Bo, Chen, Stephanie, Quinton, Anna, Cook, William, and Reddel, Helen K.

Published
2024
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57. Oligosarcomas, IDH-mutant are distinct and aggressive

Author

Suwala, Abigail K, Felix, Marius, Friedel, Dennis, Stichel, Damian, Schrimpf, Daniel, Hinz, Felix, Hewer, Ekkehard, Schweizer, Leonille, Dohmen, Hildegard, Pohl, Ute, Staszewski, Ori, Korshunov, Andrey, Stein, Marco, Wongsurawat, Thidathip, Cheunsuacchon, Pornsuk, Sathornsumetee, Sith, Koelsche, Christian, Turner, Clinton, Le Rhun, Emilie, Mühlebner, Angelika, Schucht, Philippe, Özduman, Koray, Ono, Takahiro, Shimizu, Hiroaki, Prinz, Marco, Acker, Till, Herold-Mende, Christel, Kessler, Tobias, Wick, Wolfgang, Capper, David, Wesseling, Pieter, Sahm, Felix, von Deimling, Andreas, Hartmann, Christian, and Reuss, David E

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Brain Cancer, Cancer, Brain Disorders, Clinical Research, Pediatric Research Initiative, Genetics, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Brain Neoplasms, Female, Humans, Isocitrate Dehydrogenase, Male, Middle Aged, Mutation, Oligodendroglioma, Sarcoma, Oligosarcoma, Gliosarcoma, 1p, 19q, Codeletion, SMA, YAP1, NF1, TP53, TERT, DNA methylation, Type, Subtype, Variant, Prognosis, 1p/19q, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.

Published
2022

60. The Epigenetic Landscape of Meningiomas

Author

Wang, Justin Z., Nassiri, Farshad, Aldape, Kenneth, von Deimling, Andreas, Sahm, Felix, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, Zadeh, Gelareh, editor, Goldbrunner, Roland, editor, Krischek, Boris, editor, and Nassiri, Farshad, editor

Published
2023
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61. Genetic and epigenetic characterization of posterior pituitary tumors

Author

Schmid, Simone, Solomon, David A, Perez, Eilis, Thieme, Anne, Kleinschmidt-DeMasters, Bette K, Giannini, Caterina, Reinhardt, Annekathrin, Asa, Sylvia L, Mete, Ozgur, Stichel, Damian, Siewert, Christin, Dittmayer, Carsten, Hasselblatt, Martin, Paulus, Werner, Nagel, Christoph, Harter, Patrick N, Schittenhelm, Jens, Honegger, Jürgen, Rushing, Elisabeth, Coras, Roland, Pfister, Stefan M, Buslei, Rolf, Koch, Arend, Perry, Arie, Jones, David TW, von Deimling, Andreas, Capper, David, and Lopes, M Beatriz

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Human Genome, Cancer, Aetiology, 2.1 Biological and endogenous factors, Adenoma, Oxyphilic, Epigenesis, Genetic, Granular Cell Tumor, Humans, Pituitary Neoplasms, Pituicytoma, Spindle cell oncocytoma, Granular cell tumor, Posterior pituitary gland neoplasms, Molecular neuropathology, Brain tumor, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.

Published
2021

62. Subgroup and subtype-specific outcomes in adult medulloblastoma.

Author

Coltin, Hallie, Sundaresan, Lakshmikirupa, Smith, Kyle, Skowron, Patryk, Massimi, Luca, Eberhart, Charles, Schreck, Karisa, Gupta, Nalin, Weiss, William, Tirapelli, Daniela, Carlotti, Carlos, Li, Kay, Ryzhova, Marina, Golanov, Andrey, Zheludkova, Olga, Absalyamova, Oksana, Okonechnikov, Konstantin, Stichel, Damian, von Deimling, Andreas, Giannini, Caterina, Raskin, Scott, Van Meir, Erwin, Chan, Jennifer, Fults, Daniel, Chambless, Lola, Kim, Seung-Ki, Vasiljevic, Alexandre, Faure-Conter, Cecile, Vibhakar, Rajeev, Jung, Shin, Leary, Sarah, Mora, Jaume, McLendon, Roger, Pollack, Ian, Hauser, Peter, Grajkowska, Wieslawa, Rubin, Joshua, van Veelen, Marie-Lise, French, Pim, Kros, Johan, Liau, Linda, Pfister, Stefan, Kool, Marcel, Kijima, Noriyuki, Taylor, Michael, Packer, Roger, Northcott, Paul, Korshunov, Andrey, and Ramaswamy, Vijay

Subjects
Adult, DNA methylation profiling, Medulloblastoma, Molecular groups, Risk stratification, Adolescent, Adult, Biomarkers, Tumor, Cerebellar Neoplasms, Cohort Studies, Female, Humans, Male, Medulloblastoma, Progression-Free Survival, Risk Factors, Young Adult
Abstract

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p

Published
2021

64. The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer: A Systematic Review and Meta-analysis of Prospective Studies

Author

Miszczyk, Marcin, Rajwa, Pawel, Yanagisawa, Takafumi, Nowicka, Zuzanna, Shim, Sung Ryul, Laukhtina, Ekaterina, Kawada, Tatsushi, von Deimling, Markus, Pradere, Benjamin, Rivas, Juan Gómez, Gandaglia, Giorgio, van den Bergh, Roderick C.N., Goldner, Gregor, Supiot, Stephane, Zilli, Thomas, Trinh, Quoc-Dien, Nguyen, Paul L., Briganti, Alberto, Ost, Piet, Ploussard, Guillaume, and Shariat, Shahrokh F.

Published
2024
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69. 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
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70. 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
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71. Correction to: Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

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

Published
2023
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72. Diagnostic accuracy of a minimal immunohistochemical panel in at/rt molecular subtyping, correlated to dna-methylation profiling

Author

Arnault Tauziède-Espariat, Julien Masliah-Planchon, Mamy Andrianteranagna, Philipp Sievers, Felix Sahm, Andreas von Deimling, Lauren Hasty, Olivier Delattre, Kévin Beccaria, Alice Métais, Fabrice Chrétien, Pascale Varlet, and Franck Bourdeaut

Subjects
AT/RT, DNA-methylation profiling, TYR, SHH, MYC, Immunohistochemistry., Neurology. Diseases of the nervous system, RC346-429
Published
2023
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73. Heterogeneity of DNA methylation profiles and copy number alterations in 10782 adult-type glioblastomas, IDH-wildtype

Author

David E. Reuss, Daniel Schrimpf, Asan Cherkezov, Abigail K. Suwala, Tereza Lausová, Matija Snuderl, David Capper, Martin Sill, David T. W. Jones, Stefan M. Pfister, Felix Sahm, and Andreas von Deimling

Subjects
Glioblastoma, Copy Number Variations, CNV, Methylation, Classification, 7/10 signature, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The morphological patterns leading to the diagnosis of glioblastoma may also commonly be observed in several other distinct tumor entities, which can result in a mixed bag of tumors subsumed under this diagnosis. The 2021 WHO Classification of CNS Tumors has separated several of these entities from the diagnosis of glioblastoma, IDH-wildtype. This study determines the DNA methylation classes most likely receiving the diagnosis glioblastoma, IDH wildtype according to the definition by the WHO 2021 Classification and provides comparative copy number analyses. We identified 10782 methylome datasets uploaded to the web page www.molecularneuropathology.org with a calibrated score of ≥0.9 by the Heidelberg Brain Tumor Classifier version v12.8. These methylation classes were characterized by the diagnosis glioblastoma being the most frequent classification encountered in each of the classes according to the WHO 2021 definition. Further, methylation classes selected for this study predominantly contained adult patients. Unsupervised clustering confirmed the presence of nine methylation classes containing tumors most likely receiving the diagnosis glioblastoma, IDH-wildtype according to the WHO 2021 definition. Copy number analysis and a focus on genes with typical numerical alterations in glioblastoma revealed clear differences between the nine methylation classes. Although great progress in diagnostic precision has been achieved over the last decade, our data clearly demonstrate that glioblastoma, IDH-wildtype still is a heterogeneous group in need of further stratification.

Published
2024
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74. O ENSINO DA ESPECTROSCOPIA UV-VIS NA EDUCAÇÃO BÁSICA: CONSIDERAÇÕES INICIAIS

Author

Daniel Maggioni, Natalia Neves Macedo Deimling, and Cesar Vanderlei Deimling

Subjects
interação da radiação com a matéria, espectroscopia no visível, educação básica, ensino de física, Special aspects of education, LC8-6691, Theory and practice of education, LB5-3640
Abstract

Visando colaborar na superação de alguns problemas envolvendo o ensino da Física moderna em sala de aula, neste trabalho apresentamos uma breve revisão da literatura científica tendo em vista discutir os principais resultados obtidos em trabalhos que abordam o tema de interação da radiação com a matéria, em especial aqueles que utilizam técnicas de espectroscopia usando comprimentos de onda na faixa do visível, aplicados em atividades práticas na educação básica. Trata-se da primeira etapa de uma pesquisa de mestrado, em processo inicial de desenvolvimento, vinculada ao programa de Pós-Graduação em Ensino de Física da UTFPR, campus Campo Mourão, em parceria com a Sociedade Brasileira de Física. Neste trabalho, discutimos as principais dificuldades e limitações indicadas pelas pesquisas já desenvolvidas sobre o tema, bem como os resultados positivos obtidos a partir das experiências já realizadas por professores sobre o tema em sala de aula. Partindo desses apontamentos, esperamos desenvolver um produto educacional para o ensino deste tema na educação básica que busque contribuir de maneira efetiva para a melhoria do processo de ensino-aprendizagem deste conteúdo da Física Moderna no ensino médio.

Published
2023
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76. Concurrent gliomas in patients with multiple sclerosis

Author

Sahm, Katharina, Kessler, Tobias, Eisele, Philipp, Ratliff, Miriam, Sperk, Elena, König, Laila, Breckwoldt, Michael O., Seliger, Corinna, Mildenberger, Iris, Schrimpf, Daniel, Herold-Mende, Christel, Zeiner, Pia S., Tabatabai, Ghazaleh, Meuth, Sven G., Capper, David, Bendszus, Martin, von Deimling, Andreas, Wick, Wolfgang, Sahm, Felix, and Platten, Michael

Published
2023
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79. INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas

Author

Grassl, Niklas, Sahm, Katharina, Süße, Heike, Poschke, Isabel, Bunse, Lukas, Bunse, Theresa, Boschert, Tamara, Mildenberger, Iris, Rupp, Anne-Kathleen, Ewinger, Max Philipp, Lanz, Lisa-Marie, Denk, Monika, Tabatabai, Ghazaleh, Ronellenfitsch, Michael W., Herrlinger, Ulrich, Glas, Martin, Krex, Dietmar, Vajkoczy, Peter, Wick, Antje, Harting, Inga, Sahm, Felix, von Deimling, Andreas, Bendszus, Martin, Wick, Wolfgang, and Platten, Michael

Published
2023
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81. 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
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84. Genomic characterization of DICER1-associated neoplasms uncovers molecular classes

Author

Kommoss, Felix K. F., Chong, Anne-Sophie, Chong, Anne-Laure, Pfaff, Elke, Jones, David T. W., Hiemcke-Jiwa, Laura S., Kester, Lennart A., Flucke, Uta, Gessler, Manfred, Schrimpf, Daniel, Sahm, Felix, Clarke, Blaise A., Stewart, Colin J. R., Wang, Yemin, Gilks, C. Blake, Kommoss, Friedrich, Huntsman, David G., Schüller, Ulrich, Koelsche, Christian, Glenn McCluggage, W., von Deimling, Andreas, and Foulkes, William D.

Published
2023
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86. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

Author

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

Subjects
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.

Published
2021

87. 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

88. Subsea permafrost organic carbon stocks are large and of dominantly low reactivity

Author

F. Miesner, P. P. Overduin, G. Grosse, J. Strauss, M. Langer, S. Westermann, T. Schneider von Deimling, V. Brovkin, and S. Arndt

Subjects
Medicine, Science
Abstract

Abstract Subsea permafrost carbon pools below the Arctic shelf seas are a major unknown in the global carbon cycle. We combine a numerical model of sedimentation and permafrost evolution with simplified carbon turnover to estimate accumulation and microbial decomposition of organic matter on the pan-Arctic shelf over the past four glacial cycles. We find that Arctic shelf permafrost is a globally important long-term carbon sink storing 2822 (1518–4982) Pg OC, double the amount stored in lowland permafrost. Although currently thawing, prior microbial decomposition and organic matter aging limit decomposition rates to less than 48 Tg OC/yr (25–85) constraining emissions due to thaw and suggesting that the large permafrost shelf carbon pool is largely insensitive to thaw. We identify an urgent need to reduce uncertainty in rates of microbial decomposition of organic matter in cold and saline subaquatic environments. Large emissions of methane more likely derive from older and deeper sources than from organic matter in thawing permafrost.

Published
2023
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89. Carboplatin Induction Chemotherapy in Clinically Lymph Node–positive Bladder Cancer

Author

Markus von Deimling, Laura S. Mertens, Bas W.G. van Rhijn, Yair Lotan, Philippe E. Spiess, Siamak Daneshmand, Peter C. Black, Maximilian Pallauf, David D'Andrea, Marco Moschini, Francesco Soria, Francesco Del Giudice, Luca Afferi, Ekaterina Laukhtina, Takafumi Yanagisawa, Tatsushi Kawada, Jeremy Y.-C. Teoh, Mohammad Abufaraj, Guillaume Ploussard, Mathieu Roumiguié, Pierre I. Karakiewicz, Marko Babjuk, Paolo Gontero, Evanguelos Xylinas, Michael Rink, Shahrokh F. Shariat, and Benjamin Pradere

Subjects
Carboplatin, Induction chemotherapy, Oligometastatic, Survival, Urinary bladder neoplasms, Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participants: This was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

Published
2023
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90. Spatial probabilistic mapping of metabolite ensembles in mass spectrometry imaging

Author

Denis Abu Sammour, James L. Cairns, Tobias Boskamp, Christian Marsching, Tobias Kessler, Carina Ramallo Guevara, Verena Panitz, Ahmed Sadik, Jonas Cordes, Stefan Schmidt, Shad A. Mohammed, Miriam F. Rittel, Mirco Friedrich, Michael Platten, Ivo Wolf, Andreas von Deimling, Christiane A. Opitz, Wolfgang Wick, and Carsten Hopf

Subjects
Science
Abstract

Spatial visualization of metabolites in tissues via mass spectrometry imaging can be prone to user perception bias. Here, the authors report the computational framework moleculaR that introduces probabilistic data-dependent molecular mapping of nonrandom spatial patterns of metabolite signals.

Published
2023
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93. 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

94. 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

95. 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
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97. Identification of low and very high-risk patients with non-WNT/non-SHH medulloblastoma by improved clinico-molecular stratification of the HIT2000 and I-HIT-MED cohorts

Author

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

Published
2023
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98. Understanding the perspective of community co-educators on community-based service learning: a qualitative analysis

Author

Grace Zhou, Aarabi Thayaparan, Stephanie Park, Yasamin Sadeghi, Brandi Deimling, Roxanne Wright, and Fok-Han Leung

Subjects
Education (General), L7-991, Medicine (General), R5-920
Abstract

Background: Community-based service learning (CBSL) is a core component of the Canadian medical education system. However, the unique role of community partner organizations (CPOs) in supporting CBSL remains unclear. This qualitative study evaluates the perspective of CPOs as co-educators in the undergraduate medical curriculum. Methods: We conducted eight semi-structured, one-on-one interviews with CPOs at a medical school in Toronto, Ontario between 2020-2021. Interviews were conducted following a pre-determined interview guide and then recorded, de-identified, and transcribed. Three reviewers independently performed an inductive thematic analysis of codes followed by a group review of discrepancies. Results: Five main findings were identified: 1) CPOs share a common interest in serving as co-educators; 2) considerable heterogeneity in the understanding of co-education exists; 3) there is an opportunity for increased partnerships between CPOs and faculty; 4) the role of co-educators is limited by curriculum structure; and 5) co-educators facilitate unique teachings of social determinants of health otherwise not available through traditional didactic teaching. Conclusions: There is an emerging, unique role for community co-educators in the undergraduate medical curriculum, supported by interest from CPOs. Its emphasis may contribute to future cohorts of medical students capable of understanding and addressing the needs of the populations they serve.

Published
2023
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99. Reference on copy number variations in pleomorphic xanthoastrocytoma: Implications for diagnostic approach

Author

David E. Reuss, Daniel Schrimpf, Damian Stichel, Azadeh Ebrahimi, Chris Dampier, Kenneth Aldape, Matija Snuderl, David Capper, Martin Sill, David T.W. Jones, Stefan M. Pfister, Sahm Felix, and Andreas von Deimling

Subjects
Pleomorphic Xanthoastrocytoma, PXA, Copy Number Variations, CNV, Methylation, Classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Pleomorphic xanthoastrocytoma (PXA) poses a diagnostic challenge. The present study relies on methylation-based predictions and focuses on copy number variations (CNV) in PXA. We identified 551 tumors from patients having received the histologic diagnosis or differential diagnosis pleomorphic xanthoastrocytoma (PXA) uploaded to the web page www.molecularneuropathology.org. Of these 551 tumors, 165 received the prediction “methylation class (anaplastic) pleomorphic xanthoastrocytoma” with a calibrated score >=0.9 by the brain tumor classifier version v12.8 and, therefore, were defined the PXA reference set designated mcPXAref. In addition to these 165 mcPXAref, 767 other tumors received the prediction mcPXA with a calibrated score >=0.9 but without a histological PXA diagnosis. The total number of individual tumors predicted by histology and/or by methylome based classification as PXA, mcPXA or both was 1318, and these were designated the study cohort. The selection of a control cohort was guided by methylation-based predictions recurrently observed for the other 386/551 tumors diagnosed as histologic PXA. 131/386 received predictions for another entity besides PXA with a score >=0.9. Control tumors corresponding to the 11 most common other predictions were selected, adding up to 1100 reference cases. CNV profiles were calculated from all methylation datasets of the study and control cohorts. Special attention was given to the 7/10 signature, gene amplifications and homozygous deletion of CDKN2A/B. Comparison of CNV in the subsets of the study cohort and the control cohort were used to establish relations independent of histological diagnoses. Tumors in mcPXA were highly homogenous in regard to CNV alterations, irrespective of the histological diagnoses. The 7/10 signature commonly present in glioblastoma, IDH-wildtype, was present in 15-20% of mcPXA, whereas amplification of oncogenes (likewise common in glioblastoma) was very rare in mcPXA (

Published
2023
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100. Molecular and translational advances in meningiomas

Author

Suppiah, Suganth, Nassiri, Farshad, Bi, Wenya Linda, Dunn, Ian F, Hanemann, Clemens Oliver, Horbinski, Craig M, Hashizume, Rintaro, James, Charles David, Mawrin, Christian, Noushmehr, Houtan, Perry, Arie, Sahm, Felix, Sloan, Andrew, Von Deimling, Andreas, Wen, Patrick Y, Aldape, Kenneth, Zadeh, Gelareh, Au, Karolyn, Barnhartz-Sloan, Jill, Brastianos, Priscilla K, Butowski, Nicholas, Carlotti, Carlos, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Galanis, Evanthia, Giannini, Caterina, Goldbrunner, Roland, Griffith, Brent, Hanemann, C Oliver, Herold-Mende, Christel, Horbinski, Craig, Huang, Raymond Y, James, David, Jenkinson, Michael D, Jungk, Christine, Kaufman, Timothy J, Krischek, Boris, Lachance, Daniel, Lafougère, Christian, Lee, Ian, Liu, Jeff C, Mamatjan, Yasin, Mansouri, Alireza, McDermott, Michael, Munoz, David, Ng, Ho-Keung, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Raleigh, David, Saladino, Andrea, Santarius, Thomas, Schichor, Christian, Schultz, David, Schmidt, Nils O, Selman, Warren, Spears, Julian, Snyder, James, Tabatabai, Ghazaleh, Tatagiba, Marcos, Tirapelli, Daniela, Tonn, Joerg C, Tsang, Derek, Vogelbaum, Michael A, Deimling, Andreas von, Walbert, Tobias, Westphal, Manfred, and Workewych, Adriana M

Subjects
Brain Cancer, Cancer, Brain Disorders, Rare Diseases, Human Genome, Genetics, Combined Modality Therapy, Genomics, Humans, Meningeal Neoplasms, Meningioma, Molecular Targeted Therapy, Prognosis, Translational Research, Biomedical, biomolecular, cell lines, epigenetic, genetic, sporadic meningioma, xenograft, International Consortium on Meningiomas, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

Published
2019

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