Search

Your search keyword '"Rushing, Elisabeth"' showing total 1,201 results
Start Over Author "Rushing, Elisabeth"
1,201 results on '"Rushing, Elisabeth"'

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

Author

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

Published
2024
Full Text
View/download PDF

3. A T-cell antigen atlas for meningioma: novel options for immunotherapy

Author

Medici, Gioele, Freudenmann, Lena K., Velz, Julia, Wang, Sophie Shih-Yüng, Kapolou, Konstantina, Paramasivam, Nagarajan, Mühlenbruch, Lena, Kowalewski, Daniel J., Vasella, Flavio, Bilich, Tatjana, Frey, Beat M., Dubbelaar, Marissa L., Patterson, Angelica Brooke, Zeitlberger, Anna Maria, Silginer, Manuela, Roth, Patrick, Weiss, Tobias, Wirsching, Hans-Georg, Krayenbühl, Niklaus, Bozinov, Oliver, Regli, Luca, Rammensee, Hans-Georg, Rushing, Elisabeth Jane, Sahm, Felix, Walz, Juliane S., Weller, Michael, and Neidert, Marian C.

Published
2023
Full Text
View/download PDF

4. 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

7. Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Author

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

Published
2023
Full Text
View/download PDF

12. Alterations in homologous recombination repair genes in prostate cancer brain metastases

Author

Rodriguez-Calero, Antonio, Gallon, John, Akhoundova, Dilara, Maletti, Sina, Ferguson, Alison, Cyrta, Joanna, Amstutz, Ursula, Garofoli, Andrea, Paradiso, Viola, Tomlins, Scott A., Hewer, Ekkehard, Genitsch, Vera, Fleischmann, Achim, Vassella, Erik, Rushing, Elisabeth J., Grobholz, Rainer, Fischer, Ingeborg, Jochum, Wolfram, Cathomas, Gieri, Osunkoya, Adeboye O., Bubendorf, Lukas, Moch, Holger, Thalmann, George, Ng, Charlotte K. Y., Gillessen, Silke, Piscuoglio, Salvatore, and Rubin, Mark A.

Published
2022
Full Text
View/download PDF

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

Author

Capper, David, Jones, David TW, Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E, Kratz, Annekathrin, Wefers, Annika K, Huang, Kristin, Pajtler, Kristian W, Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W, Lindenberg, Kerstin, Harter, Patrick N, Braczynski, Anne K, Plate, Karl H, Dohmen, Hildegard, Garvalov, Boyan K, Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J, Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R, Kohlhof, Patricia, Kristensen, Bjarne W, Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G, Driever, Pablo Hernáiz, Kramm, Christof M, Müller, Hermann L, Rutkowski, Stefan, von Hoff, Katja, Frühwald, Michael C, Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, and Jones, Chris

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

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

Published
2018

16. Expanding the spectrum of low‐grade sinonasal adenocarcinoma with biphasic seromucinous differentiation and activating HRAS/AKT1 mutations.

Author

Hadnagy, Viktoria S, Körner, Meike, Rössle, Matthias, Dubach, Patrick, Pabst, Gunther, Kotulova, Alexandra, Weder, Stefan, Seifert, Robert, Rushing, Elisabeth J, Holzmann, David, Hüllner, Martin, Freiberger, Sandra N, and Rupp, Niels J

Abstract

Aims: Low‐grade non‐intestinal‐type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal‐ and salivary‐type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification. Methods and results: Clinical, histological and molecular characterisation of four cases of biphasic, low‐grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo‐glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in‐situ/precursor lesions adjacent to the tumour. Follow‐up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years. Conclusion: This study further corroborates a distinct biphasic low‐grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial–myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

25. YAP1-fusions in pediatric NF2-wildtype meningioma

Author

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

Published
2020
Full Text
View/download PDF

27. International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading.

Author

Louis, David N, Perry, Arie, Burger, Peter, Ellison, David W, Reifenberger, Guido, von Deimling, Andreas, Aldape, Kenneth, Brat, Daniel, Collins, V Peter, Eberhart, Charles, Figarella-Branger, Dominique, Fuller, Gregory N, Giangaspero, Felice, Giannini, Caterina, Hawkins, Cynthia, Kleihues, Paul, Korshunov, Andrey, Kros, Johan M, Beatriz Lopes, M, Ng, Ho-Keung, Ohgaki, Hiroko, Paulus, Werner, Pietsch, Torsten, Rosenblum, Marc, Rushing, Elisabeth, Soylemezoglu, Figen, Wiestler, Otmar, Wesseling, Pieter, and International Society Of Neuropathology--Haarlem

Subjects
International Society Of Neuropathology--Haarlem, Humans, Nervous System Neoplasms, Molecular Diagnostic Techniques, Severity of Illness Index, Astrocytoma, World Health Organization, atypical teratoid rhabdoid tumor, brain tumors, classification, glioblastoma, glioma, grading, medulloblastoma, oligodendroglioma, Neurology & Neurosurgery, Clinical Sciences, Neurosciences
Abstract

Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.

Published
2014

28. ISN‐Haarlem Brain Tumor Classification Guidelines

Author

Louis, David N, Perry, Arie, Burger, Peter, Ellison, David W, Reifenberger, Guido, von Deimling, Andreas, Aldape, Kenneth, Brat, Daniel, Collins, V Peter, Eberhart, Charles, Figarella‐Branger, Dominique, Fuller, Gregory N, Giangaspero, Felice, Giannini, Caterina, Hawkins, Cynthia, Kleihues, Paul, Korshunov, Andrey, Kros, Johan M, Lopes, M Beatriz, Ng, Ho‐Keung, Ohgaki, Hiroko, Paulus, Werner, Pietsch, Torsten, Rosenblum, Marc, Rushing, Elisabeth, Soylemezoglu, Figen, Wiestler, Otmar, and Wesseling, Pieter

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Rare Diseases, Brain Cancer, Neurosciences, Cancer, Humans, Molecular Diagnostic Techniques, Nervous System Neoplasms, Severity of Illness Index, Astrocytoma, atypical teratoid rhabdoid tumor, brain tumors, classification, glioblastoma, glioma, grading, medulloblastoma, oligodendroglioma, World Health Organization, International Society Of Neuropathology--Haarlem, Neurology & Neurosurgery, Clinical sciences
Abstract

Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.

Published
2014

29. A prognostic model for tumor recurrence and progression after meningioma surgery: preselection for further molecular work-up

Author

Padevit, Luis, primary, Vasella, Flavio, additional, Friedman, Jason, additional, Mutschler, Valentino, additional, Jenkins, Freya, additional, Held, Ulrike, additional, Rushing, Elisabeth Jane, additional, Wirsching, Hans-Georg, additional, Weller, Michael, additional, Regli, Luca, additional, and Neidert, Marian Christoph, additional

Published
2023
Full Text
View/download PDF

30. Diagnostic value of 18F-fluordesoxyglucose positron emission tomography for patients with brain metastasis from unknown primary site

Author

Wolpert, Fabian, Weller, Michael, Berghoff, Anna Sophie, Rushing, Elisabeth, Füreder, Lisa Michaela, Petyt, Gregory, Leske, Henning, Andratschke, Nicolaus, Regli, Luca, Neidert, Marian Christoph, Stupp, Roger, Stahel, Rolf, Dummer, Reinhard, Frauenfelder, Thomas, Roth, Patrick, Reyns, Nicolas, Kaufmann, Philipp Antonio, Preusser, Matthias, and Le Rhun, Emilie

Published
2018
Full Text
View/download PDF

31. Rosette-forming glioneuronal tumors share a distinct DNA methylation profile and mutations in FGFR1, with recurrent co-mutation of PIK3CA and NF1

Author

Sievers, Philipp, Appay, Romain, Schrimpf, Daniel, Stichel, Damian, Reuss, David E., Wefers, Annika K., Reinhardt, Annekathrin, Coras, Roland, Ruf, Viktoria C., Schmid, Simone, de Stricker, Karin, Boldt, Henning B., Kristensen, Bjarne Winther, Petersen, Jeanette Krogh, Ulhøi, Benedicte P., Gardberg, Maria, Aronica, Eleonora, Hasselblatt, Martin, Brück, Wolfgang, Bielle, Franck, Mokhtari, Karima, Lhermitte, Benoît, Wick, Wolfgang, Herold-Mende, Christel, Hänggi, Daniel, Brandner, Sebastian, Giangaspero, Felice, Capper, David, Rushing, Elisabeth, Wesseling, Pieter, Pfister, Stefan M., Figarella-Branger, Dominique, von Deimling, Andreas, Sahm, Felix, and Jones, David T. W.

Published
2019
Full Text
View/download PDF

32. A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis

Author

Johnson, Douglas B., McDonnell, Wyatt J., Gonzalez-Ericsson, Paula I., Al-Rohil, Rami N., Mobley, Bret C., Salem, Joe-Elie, Wang, Daniel Y., Sanchez, Violeta, Wang, Yu, Chastain, Cody A., Barker, Kristi, Liang, Yan, Warren, Sarah, Beechem, Joseph M., Menzies, Alexander M., Tio, Martin, Long, Georgina V., Cohen, Justine V., Guidon, Amanda C., O’Hare, Méabh, Chandra, Sunandana, Chowdhary, Akansha, Lebrun-Vignes, Bénédicte, Goldinger, Simone M., Rushing, Elisabeth J., Buchbinder, Elizabeth I., Mallal, Simon A., Shi, Chanjuan, Xu, Yaomin, Moslehi, Javid J., Sanders, Melinda E., Sosman, Jeffrey A., and Balko, Justin M.

Published
2019
Full Text
View/download PDF

35. Primary spinal cord tumors of childhood: effects of clinical presentation, radiographic features, and pathology on survival

Author

Crawford, John R., Zaninovic, Alejandra, Santi, Mariarita, Rushing, Elisabeth J., Olsen, Cara H., Keating, Robert F., Vezina, Gilbert, Kadom, Nadja, and Packer, Roger J.

Subjects
Medicine & Public Health, Neurology, Oncology, Pediatric spinal cord tumor, Intraspinal tumor, Childhood spinal tumor
Abstract

To determine the relationship between clinical presentation, radiographic features, pathology, and treatment on overall survival of newly diagnosed pediatric primary spinal cord tumors (PSCT). Retrospective analysis of all previously healthy children with newly diagnosed PSCT at a single institution from 1995 to present was performed. Twenty-five pediatric patients (15 boys, average 7.9 years) were diagnosed with PSCT. Presenting symptoms ranged from 0.25 to 60 months (average 7.8 months). Symptom duration was significantly shorter for high grade tumors (average 1.65 months) than low grade tumors (average 11.2 months) (P = 0.05). MRI revealed tumor (8 cervical, 17 thoracic, 7 lumbar, 7 sacral) volumes of 98–94,080 mm3 (average 19,474 mm3). Homogeneous gadolinium enhancement on MRI correlated with lower grade pathology (P = 0.003). There was no correlation between tumor grade and volume (P = 0.63) or edema (P = 0.36) by MRI analysis. Median survival was 53 months and was dependent on tumor grade (P = 0.05) and gross total resection (P = 0.01) but not on gender (P = 0.49), age of presentation (P = 0.82), duration of presenting symptoms (P = 0.33), or adjuvant therapies (P = 0.17). Stratified Kaplan–Meier analysis confirmed the association between degree of resection and survival after controlling for tumor grade (P = 0.01). MRI homogeneous gadolinium enhancement patterns may be helpful in distinguishing low grade from high grade spinal cord malignancies. While tumor grade and gross total resection rather than duration of symptoms correlated with survival in our series, greater than one-third of patients had reported symptoms greater than 6 months duration prior to diagnosis.

Published
2009

36. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis

Author

Sahm, Felix, Schrimpf, Daniel, Stichel, Damian, Jones, David T W, Hielscher, Thomas, Schefzyk, Sebastian, Okonechnikov, Konstantin, Koelsche, Christian, Reuss, David E, Capper, David, Sturm, Dominik, Wirsching, Hans-Georg, Berghoff, Anna Sophie, Baumgarten, Peter, Kratz, Annekathrin, Huang, Kristin, Wefers, Annika K, Hovestadt, Volker, Sill, Martin, Ellis, Hayley P, Kurian, Kathreena M, Okuducu, Ali Fuat, Jungk, Christine, Drueschler, Katharina, Schick, Matthias, Bewerunge-Hudler, Melanie, Mawrin, Christian, Seiz-Rosenhagen, Marcel, Ketter, Ralf, Simon, Matthias, Westphal, Manfred, Lamszus, Katrin, Becker, Albert, Koch, Arend, Schittenhelm, Jens, Rushing, Elisabeth J, Collins, V Peter, Brehmer, Stefanie, Chavez, Lukas, Platten, Michael, Hänggi, Daniel, Unterberg, Andreas, Paulus, Werner, Wick, Wolfgang, Pfister, Stefan M, Mittelbronn, Michel, Preusser, Matthias, Herold-Mende, Christel, Weller, Michael, and von Deimling, Andreas

Published
2017
Full Text
View/download PDF

39. Data from DNA Methylation Landscapes of Prostate Cancer Brain Metastasis Are Shaped by Early Driver Genetic Alterations

Author

Gallon, John, primary, Rodriguez-Calero, Antonio, primary, Benjak, Andrej, primary, Akhoundova, Dilara, primary, Maletti, Sina, primary, Amstutz, Ursula, primary, Hewer, Ekkehard, primary, Genitsch, Vera, primary, Fleischmann, Achim, primary, Rushing, Elisabeth J., primary, Grobholz, Rainer, primary, Fischer, Ingeborg, primary, Jochum, Wolfram, primary, Cathomas, Gieri, primary, Osunkoya, Adeboye O., primary, Bubendorf, Lukas, primary, Moch, Holger, primary, Thalmann, George, primary, Feng, Felix Y., primary, Gillessen, Silke, primary, Ng, Charlotte K.Y., primary, Rubin, Mark A., primary, and Piscuoglio, Salvatore, primary

Published
2023
Full Text
View/download PDF

40. Supplementary Data from DNA Methylation Landscapes of Prostate Cancer Brain Metastasis Are Shaped by Early Driver Genetic Alterations

Author

Gallon, John, primary, Rodriguez-Calero, Antonio, primary, Benjak, Andrej, primary, Akhoundova, Dilara, primary, Maletti, Sina, primary, Amstutz, Ursula, primary, Hewer, Ekkehard, primary, Genitsch, Vera, primary, Fleischmann, Achim, primary, Rushing, Elisabeth J., primary, Grobholz, Rainer, primary, Fischer, Ingeborg, primary, Jochum, Wolfram, primary, Cathomas, Gieri, primary, Osunkoya, Adeboye O., primary, Bubendorf, Lukas, primary, Moch, Holger, primary, Thalmann, George, primary, Feng, Felix Y., primary, Gillessen, Silke, primary, Ng, Charlotte K.Y., primary, Rubin, Mark A., primary, and Piscuoglio, Salvatore, primary

Published
2023
Full Text
View/download PDF

41. Supplementary Tables 1, 3, 5-7 from Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma

Author

Wang, Jian, primary, Weiss, Tobias, primary, Neidert, Marian C., primary, Toussaint, Nora C., primary, Naghavian, Reza, primary, Sellés Moreno, Carla, primary, Foege, Magdalena, primary, Tomas Ojer, Paula, primary, Medici, Gioele, primary, Jelcic, Ivan, primary, Schulz, Daniel, primary, Rushing, Elisabeth, primary, Dettwiler, Susanne, primary, Schrörs, Barbara, primary, Shin, Joo Heon, primary, McKay, Ron, primary, Wu, Catherine J., primary, Lutterotti, Andreas, primary, Sospedra, Mireia, primary, Moch, Holger, primary, Greiner, Erich F., primary, Bodenmiller, Bernd, primary, Regli, Luca, primary, Weller, Michael, primary, Roth, Patrick, primary, and Martin, Roland, primary

Published
2023
Full Text
View/download PDF

42. Table S2 from Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma

Author

Wang, Jian, primary, Weiss, Tobias, primary, Neidert, Marian C., primary, Toussaint, Nora C., primary, Naghavian, Reza, primary, Sellés Moreno, Carla, primary, Foege, Magdalena, primary, Tomas Ojer, Paula, primary, Medici, Gioele, primary, Jelcic, Ivan, primary, Schulz, Daniel, primary, Rushing, Elisabeth, primary, Dettwiler, Susanne, primary, Schrörs, Barbara, primary, Shin, Joo Heon, primary, McKay, Ron, primary, Wu, Catherine J., primary, Lutterotti, Andreas, primary, Sospedra, Mireia, primary, Moch, Holger, primary, Greiner, Erich F., primary, Bodenmiller, Bernd, primary, Regli, Luca, primary, Weller, Michael, primary, Roth, Patrick, primary, and Martin, Roland, primary

Published
2023
Full Text
View/download PDF

43. Long-term survival with IDH wildtype glioblastoma:first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Author

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, Weller, Michael, 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

Abstract

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich. Results: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24–78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9–11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours. Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma.

Published
2023

44. Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Author

Hertler, Caroline; https://orcid.org/0000-0001-6181-2895, Felsberg, Jörg, Gramatzki, Dorothee; https://orcid.org/0000-0002-9054-5498, Le Rhun, Emilie; https://orcid.org/0000-0002-9408-3278, Clarke, Jennifer; https://orcid.org/0000-0002-8054-7342, Soffietti, Riccardo; https://orcid.org/0000-0002-9204-7038, Wick, Wolfgang, Chinot, Olivier, Ducray, François, Roth, Patrick, McDonald, Kerrie, Hau, Peter, Hottinger, Andreas F, Reijneveld, Jaap, Schnell, Oliver; https://orcid.org/0000-0002-1284-1427, Marosi, Christine, Glantz, Michael, Darlix, Amélie, Lombardi, Giuseppe, Krex, Dietmar, Glas, Martin, Reardon, David A, van den Bent, Martin; https://orcid.org/0000-0001-5710-5127, Lefranc, Florence, Herrlinger, Ulrich, Razis, Evangelia, Carpentier, Antoine F, Phillips, Samuel, Rudà, Roberta, Wick, Antje, et al, Rushing, Elisabeth; https://orcid.org/0000-0001-7616-6320, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Hertler, Caroline; https://orcid.org/0000-0001-6181-2895, Felsberg, Jörg, Gramatzki, Dorothee; https://orcid.org/0000-0002-9054-5498, Le Rhun, Emilie; https://orcid.org/0000-0002-9408-3278, Clarke, Jennifer; https://orcid.org/0000-0002-8054-7342, Soffietti, Riccardo; https://orcid.org/0000-0002-9204-7038, Wick, Wolfgang, Chinot, Olivier, Ducray, François, Roth, Patrick, McDonald, Kerrie, Hau, Peter, Hottinger, Andreas F, Reijneveld, Jaap, Schnell, Oliver; https://orcid.org/0000-0002-1284-1427, Marosi, Christine, Glantz, Michael, Darlix, Amélie, Lombardi, Giuseppe, Krex, Dietmar, Glas, Martin, Reardon, David A, van den Bent, Martin; https://orcid.org/0000-0001-5710-5127, Lefranc, Florence, Herrlinger, Ulrich, Razis, Evangelia, Carpentier, Antoine F, Phillips, Samuel, Rudà, Roberta, Wick, Antje, et al, Rushing, Elisabeth; https://orcid.org/0000-0001-7616-6320, and Weller, Michael; https://orcid.org/0000-0002-1748-174X

Abstract

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich. Results: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours. Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma.

Published
2023

45. MGMT methylation pattern of long-term and short-term survivors of glioblastoma reveals CpGs of the enhancer region to be of high prognostic value

Author

Leske, Henning; https://orcid.org/0000-0002-3057-8730, Camenisch Gross, Ulrike, Hofer, Silvia, Neidert, Marian Christoph; https://orcid.org/0000-0003-2828-4706, Leske, Sabine, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Lehnick, Dirk, Rushing, Elisabeth Jane, Leske, Henning; https://orcid.org/0000-0002-3057-8730, Camenisch Gross, Ulrike, Hofer, Silvia, Neidert, Marian Christoph; https://orcid.org/0000-0003-2828-4706, Leske, Sabine, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Lehnick, Dirk, and Rushing, Elisabeth Jane

Abstract

Treatment with the alkylating agent temozolomide is known to be prognostically beneficial in a subset of glioblastoma patients. Response to such chemotherapeutic treatment and the prognostic benefit have been linked to the methylation status of O$^{6}$-methylguanine-DNA methyltransferase (MGMT). To date, it has not been entirely resolved which methylation pattern of MGMT is most relevant to predict response to temozolomide treatment and outcome. In this retrospective study, we compared the methylation patterns, analyzed by Sanger sequencing, of 27 isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients that survived more than 3 years (long-term survivors) with those of 24 patients who survived less than a year after initial surgery (short-term survivors). Random Forest-, Correlation-, and ROC-curve analyses were performed. The data showed that MGMT is typically methylated in long-term survivors, whereas no prominent methylation is observed in short-term survivors. The methylation status of CpGs, especially in the promoter and exon1/enhancer region correlated highly with outcome. In addition, age and temozolomide treatment were strongly associated with overall survival. Some CpGs in the enhancer region, in particular CpG 86 (bp + 154), demonstrated high values associated with overall survival in the Random Forest analysis. Our data confirm previously published prognostic factors in IDH-wildtype glioblastoma patients, including age and temozolomide treatment as well as the global MGMT methylation status. The area frequently used for decision making to administer temozolomide at the end of exon1 of MGMT, was associated with outcome. However, our data also suggest that the enhancer region, especially CpG 86 (bp + 154) is of strong prognostic value. Therefore, we propose further investigation of the enhancer region in a large prospective study in order to confirm our findings, which might result in an optimized prediction of survival in glioblastoma patients, likel

Published
2023

46. A prognostic model for tumor recurrence and progression after meningioma surgery: preselection for further molecular work-up

Author

Padevit, Luis, Vasella, Flavio; https://orcid.org/0000-0002-8953-0862, Friedman, Jason, Mutschler, Valentino, Jenkins, Freya, Held, Ulrike; https://orcid.org/0000-0003-3105-5840, Rushing, Elisabeth Jane, Wirsching, Hans-Georg; https://orcid.org/0000-0001-6254-4204, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Regli, Luca; https://orcid.org/0000-0003-4639-4474, Neidert, Marian Christoph; https://orcid.org/0000-0003-2828-4706, Padevit, Luis, Vasella, Flavio; https://orcid.org/0000-0002-8953-0862, Friedman, Jason, Mutschler, Valentino, Jenkins, Freya, Held, Ulrike; https://orcid.org/0000-0003-3105-5840, Rushing, Elisabeth Jane, Wirsching, Hans-Georg; https://orcid.org/0000-0001-6254-4204, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Regli, Luca; https://orcid.org/0000-0003-4639-4474, and Neidert, Marian Christoph; https://orcid.org/0000-0003-2828-4706

Abstract

PURPOSE: The selection of patients for further therapy after meningioma surgery remains a challenge. Progress has been made in this setting in selecting patients that are more likely to have an aggressive disease course by using molecular tests such as gene panel sequencing and DNA methylation profiling. The aim of this study was to create a preselection tool warranting further molecular work-up. METHODS: All patients undergoing surgery for resection or biopsy of a cranial meningioma from January 2013 until December 2018 at the University Hospital Zurich with available tumor histology were included. Various prospectively collected clinical, radiological, histological and immunohistochemical variables were analyzed and used to train a logistic regression model to predict tumor recurrence or progression. Regression coefficients were used to generate a scoring system grading every patient into low, intermediate, and high-risk group for tumor progression or recurrence. RESULTS: Out of a total of 13 variables preselected for this study, previous meningioma surgery, Simpson grade, progesterone receptor staining as well as presence of necrosis and patternless growth on histopathological analysis of 378 patients were included into the final model. Discrimination showed an AUC of 0.81 (95% CI 0.73 - 0.88), the model was well-calibrated. Recurrence-free survival was significantly decreased in patients in intermediate and high-risk score groups (p-value < 0.001). CONCLUSION: The proposed prediction model showed good discrimination and calibration. This prediction model is based on easily obtainable information and can be used as an adjunct for patient selection for further molecular work-up in a tertiary hospital setting.

Published
2023

47. DNA Methylation Landscapes of Prostate Cancer Brain Metastasis Are Shaped by Early Driver Genetic Alterations

Author

Gallon, John; https://orcid.org/0000-0002-5328-6298, Rodriguez-Calero, Antonio; https://orcid.org/0000-0002-2744-2381, Benjak, Andrej; https://orcid.org/0000-0003-4522-6575, Akhoundova, Dilara; https://orcid.org/0000-0003-1639-3059, Maletti, Sina; https://orcid.org/0000-0002-8678-0321, Amstutz, Ursula; https://orcid.org/0000-0002-0880-456X, Hewer, Ekkehard; https://orcid.org/0000-0002-9128-0364, Genitsch, Vera; https://orcid.org/0000-0003-1476-9980, Fleischmann, Achim; https://orcid.org/0000-0002-2894-4201, Rushing, Elisabeth J; https://orcid.org/0000-0001-7616-6320, Grobholz, Rainer; https://orcid.org/0000-0002-1901-7967, Fischer, Ingeborg; https://orcid.org/0000-0002-7659-3899, Jochum, Wolfram; https://orcid.org/0000-0001-6170-2020, Cathomas, Gieri; https://orcid.org/0000-0003-1276-4940, Osunkoya, Adeboye O; https://orcid.org/0000-0001-5712-8134, Bubendorf, Lukas; https://orcid.org/0000-0001-5970-1803, Moch, Holger; https://orcid.org/0000-0002-7986-2839, Thalmann, George; https://orcid.org/0000-0002-1908-3286, Feng, Felix Y; https://orcid.org/0000-0002-0963-7687, Gillessen, Silke; https://orcid.org/0000-0001-5746-6555, Ng, Charlotte K Y; https://orcid.org/0000-0002-6100-0026, Rubin, Mark A; https://orcid.org/0000-0002-8321-9950, Piscuoglio, Salvatore; https://orcid.org/0000-0003-2686-2939, Gallon, John; https://orcid.org/0000-0002-5328-6298, Rodriguez-Calero, Antonio; https://orcid.org/0000-0002-2744-2381, Benjak, Andrej; https://orcid.org/0000-0003-4522-6575, Akhoundova, Dilara; https://orcid.org/0000-0003-1639-3059, Maletti, Sina; https://orcid.org/0000-0002-8678-0321, Amstutz, Ursula; https://orcid.org/0000-0002-0880-456X, Hewer, Ekkehard; https://orcid.org/0000-0002-9128-0364, Genitsch, Vera; https://orcid.org/0000-0003-1476-9980, Fleischmann, Achim; https://orcid.org/0000-0002-2894-4201, Rushing, Elisabeth J; https://orcid.org/0000-0001-7616-6320, Grobholz, Rainer; https://orcid.org/0000-0002-1901-7967, Fischer, Ingeborg; https://orcid.org/0000-0002-7659-3899, Jochum, Wolfram; https://orcid.org/0000-0001-6170-2020, Cathomas, Gieri; https://orcid.org/0000-0003-1276-4940, Osunkoya, Adeboye O; https://orcid.org/0000-0001-5712-8134, Bubendorf, Lukas; https://orcid.org/0000-0001-5970-1803, Moch, Holger; https://orcid.org/0000-0002-7986-2839, Thalmann, George; https://orcid.org/0000-0002-1908-3286, Feng, Felix Y; https://orcid.org/0000-0002-0963-7687, Gillessen, Silke; https://orcid.org/0000-0001-5746-6555, Ng, Charlotte K Y; https://orcid.org/0000-0002-6100-0026, Rubin, Mark A; https://orcid.org/0000-0002-8321-9950, and Piscuoglio, Salvatore; https://orcid.org/0000-0003-2686-2939

Abstract

UNLABELLED Metastases from primary prostate cancers to rare locations, such as the brain, are becoming more common due to longer life expectancy resulting from improved treatments. Epigenetic dysregulation is a feature of primary prostate cancer, and distinct DNA methylation profiles have been shown to be associated with the mutually exclusive SPOP-mutant or TMPRSS2-ERG fusion genetic backgrounds. Using a cohort of prostate cancer brain metastases (PCBM) from 42 patients, with matched primary tumors for 17 patients, we carried out a DNA methylation analysis to examine the epigenetic distinction between primary prostate cancer and PCBM, the association between epigenetic alterations and mutational background, and particular epigenetic alterations that may be associated with PCBM. Multiregion sampling of PCBM revealed epigenetic stability within metastases. Aberrant methylation in PCBM was associated with mutational background and PRC2 complex activity, an effect that is particularly pronounced in SPOP-mutant PCBM. While PCBM displayed a CpG island hypermethylator phenotype, hypomethylation at the promoters of genes involved in neuroactive ligand-receptor interaction and cell adhesion molecules such as GABRB3, CLDN8, and CLDN4 was also observed, suggesting that cells from primary tumors may require specific reprogramming to form brain metastasis. This study revealed the DNA methylation landscapes of PCBM and the potential mechanisms and effects of PCBM-associated aberrant DNA methylation. SIGNIFICANCE DNA methylation analysis reveals the molecular characteristics of PCBM and may serve as a starting point for efforts to identify and target susceptibilities of these rare metastases.

Published
2023

48. A T-cell antigen atlas for meningioma: novel options for immunotherapy

Author

Medici, Gioele; https://orcid.org/0000-0003-2279-6014, Freudenmann, Lena K, Velz, Julia; https://orcid.org/0000-0001-8027-9918, Wang, Sophie Shih-Yüng, Kapolou, Konstantina, Paramasivam, Nagarajan; https://orcid.org/0000-0002-7126-8472, Mühlenbruch, Lena, Kowalewski, Daniel J, Vasella, Flavio; https://orcid.org/0000-0002-8953-0862, Bilich, Tatjana, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Dubbelaar, Marissa L, Patterson, Angelica Brooke, Zeitlberger, Anna Maria, Silginer, Manuela; https://orcid.org/0000-0003-2538-1244, Roth, Patrick; https://orcid.org/0000-0003-3897-214X, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Wirsching, Hans-Georg; https://orcid.org/0000-0001-6254-4204, Krayenbühl, Niklaus; https://orcid.org/0000-0002-4973-7527, Bozinov, Oliver; https://orcid.org/0000-0002-4620-3992, Regli, Luca; https://orcid.org/0000-0003-4639-4474, Rammensee, Hans-Georg, Rushing, Elisabeth Jane, Sahm, Felix; https://orcid.org/0000-0001-5441-1962, Walz, Juliane S; https://orcid.org/0000-0001-6404-7391, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Neidert, Marian C; https://orcid.org/0000-0003-2828-4706, Medici, Gioele; https://orcid.org/0000-0003-2279-6014, Freudenmann, Lena K, Velz, Julia; https://orcid.org/0000-0001-8027-9918, Wang, Sophie Shih-Yüng, Kapolou, Konstantina, Paramasivam, Nagarajan; https://orcid.org/0000-0002-7126-8472, Mühlenbruch, Lena, Kowalewski, Daniel J, Vasella, Flavio; https://orcid.org/0000-0002-8953-0862, Bilich, Tatjana, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Dubbelaar, Marissa L, Patterson, Angelica Brooke, Zeitlberger, Anna Maria, Silginer, Manuela; https://orcid.org/0000-0003-2538-1244, Roth, Patrick; https://orcid.org/0000-0003-3897-214X, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Wirsching, Hans-Georg; https://orcid.org/0000-0001-6254-4204, Krayenbühl, Niklaus; https://orcid.org/0000-0002-4973-7527, Bozinov, Oliver; https://orcid.org/0000-0002-4620-3992, Regli, Luca; https://orcid.org/0000-0003-4639-4474, Rammensee, Hans-Georg, Rushing, Elisabeth Jane, Sahm, Felix; https://orcid.org/0000-0001-5441-1962, Walz, Juliane S; https://orcid.org/0000-0001-6404-7391, Weller, Michael; https://orcid.org/0000-0002-1748-174X, and Neidert, Marian C; https://orcid.org/0000-0003-2828-4706

Abstract

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

Published
2023

49. Gustatory Function of Patients With and Without Cholesteatoma Undergoing Middle Ear Surgery

Author

Neumann, Aline Sophie; https://orcid.org/0000-0002-2140-9505, Soyka, Michael B, Rushing, Elisabeth J, Röösli, Christof, Neumann, Aline Sophie; https://orcid.org/0000-0002-2140-9505, Soyka, Michael B, Rushing, Elisabeth J, and Röösli, Christof

Abstract

Objective: To compare measured and perceived taste function before and after surgery of patients with chronic otitis media with cholesteatoma (OMCC) to patients without cholesteatoma (patients with chronic suppurative otitis media [CSOM] and patients with lateral skull base lesions [LSB]). Methods: This prospective cohort study included 29 patients undergoing surgery for unilateral OMCC. The chorda tympani nerve (CTN) was resected in 8 of these patients. Fourteen patients undergoing surgery for unilateral CSOM and 5 patients undergoing surgery for unilateral LSB (with CTN resection) served as the comparison group. Taste function was measured using taste strips on both sides of the tongue before surgery, 2 weeks postoperatively and 3 months postoperatively. The affected side of the tongue was compared to the unaffected side. A questionnaire on taste perception was completed at each visit. Results: Preoperatively, cholesteatoma patients showed higher taste strip scores than non-cholesteatoma patients, indicating a larger difference between the healthy and affected sides of the tongue. Despite this difference in measured taste function few cholesteatoma patients reported taste alteration before surgery (3/29 [10.3%]). Postoperatively, patients with CTN resection (OMCC patients with CTN resection and LSB patients) showed a decreased measured taste function. Subjectively, only approximately 20% of these patients reported taste alteration 3 months postoperatively. Conclusions: Before surgery, cholesteatoma patients displayed an impaired measured taste function compared to patients without cholesteatoma (CSOM, LSB). Subjectively this was often unnoticed. After surgery, despite removal of the CTN and consequent reduction of measured taste function, few patients reported taste alteration and subjective taste perception was seen to be improving. In regards to middle ear surgery, perceived taste function does not seem to reflect measured gustatory function.

Published
2023

50. High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity

Author

Lee, Sohyon, Weiss, Tobias, Bühler, Marcel, Mena, Julien, Lottenbach, Zuzanna, Wegmann, Rebekka, Sun, Miaomiao, Bihl, Michel, Augustynek, Bartłomiej, Baumann, Sven P., Goetze, Sandra, van Drogen, Audrey, Pedrioli, Patrick G. A., Penton, David, Festl, Yasmin, Buck, Alicia, Kirschenbaum, Daniel, Zeitlberger, Anna M., Neidert, Marian C., Vasella, Flavio, Rushing, Elisabeth J., Wollscheid, Bernd, Hediger, Matthias A., Weller, Michael, and Snijder, Berend

Abstract

Glioblastoma, the most aggressive primary brain cancer, has a dismal prognosis, yet systemic treatment is limited to DNA-alkylating chemotherapies. New therapeutic strategies may emerge from exploring neurodevelopmental and neurophysiological vulnerabilities of glioblastoma. To this end, we systematically screened repurposable neuroactive drugs in glioblastoma patient surgery material using a clinically concordant and single-cell resolved platform. Profiling more than 2,500 ex vivo drug responses across 27 patients and 132 drugs identified class-diverse neuroactive drugs with potent anti-glioblastoma efficacy that were validated across model systems. Interpretable molecular machine learning of drug–target networks revealed neuroactive convergence on AP-1/BTG-driven glioblastoma suppression, enabling expanded in silico screening of more than 1 million compounds with high patient validation accuracy. Deep multimodal profiling confirmed Ca2+-driven AP-1/BTG-pathway induction as a neuro-oncological glioblastoma vulnerability, epitomized by the anti-depressant vortioxetine synergizing with current standard-of-care chemotherapies in vivo. These findings establish an actionable framework for glioblastoma treatment rooted in its neural etiology.

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results