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113 results on '"Bluemcke, Ingmar"'

1. MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma

Author

Friker, Lea L., Perwein, Thomas, Waha, Andreas, Dörner, Evelyn, Klein, Rebecca, Blattner-Johnson, Mirjam, Layer, Julian P., Sturm, Dominik, Nussbaumer, Gunther, Kwiecien, Robert, Spier, Isabel, Aretz, Stefan, Kerl, Kornelius, Hennewig, Ulrike, Rohde, Marius, Karow, Axel, Bluemcke, Ingmar, Schmitz, Ann Kristin, Reinhard, Harald, Hernáiz Driever, Pablo, Wendt, Susanne, Weiser, Annette, Guerreiro Stücklin, Ana S., Gerber, Nicolas U., von Bueren, André O., Khurana, Claudia, Jorch, Norbert, Wiese, Maria, Kratz, Christian P., Eyrich, Matthias, Karremann, Michael, Herrlinger, Ulrich, Hölzel, Michael, Jones, David T. W., Hoffmann, Marion, Pietsch, Torsten, Gielen, Gerrit H., and Kramm, Christof M.

Published
2025
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3. Automatic and explainable grading of meningiomas from histopathology images

Author

Ganz, Jonathan, Kirsch, Tobias, Hoffmann, Lucas, Bertram, Christof A., Hoffmann, Christoph, Maier, Andreas, Breininger, Katharina, Blümcke, Ingmar, Jabari, Samir, and Aubreville, Marc

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, 68T99
Abstract

Meningioma is one of the most prevalent brain tumors in adults. To determine its malignancy, it is graded by a pathologist into three grades according to WHO standards. This grade plays a decisive role in treatment, and yet may be subject to inter-rater discordance. In this work, we present and compare three approaches towards fully automatic meningioma grading from histology whole slide images. All approaches are following a two-stage paradigm, where we first identify a region of interest based on the detection of mitotic figures in the slide using a state-of-the-art object detection deep learning network. This region of highest mitotic rate is considered characteristic for biological tumor behavior. In the second stage, we calculate a score corresponding to tumor malignancy based on information contained in this region using three different settings. In a first approach, image patches are sampled from this region and regression is based on morphological features encoded by a ResNet-based network. We compare this to learning a logistic regression from the determined mitotic count, an approach which is easily traceable and explainable. Lastly, we combine both approaches in a single network. We trained the pipeline on 951 slides from 341 patients and evaluated them on a separate set of 141 slides from 43 patients. All approaches yield a high correlation to the WHO grade. The logistic regression and the combined approach had the best results in our experiments, yielding correct predictions in 32 and 33 of all cases, respectively, with the image-based approach only predicting 25 cases correctly. Spearman's correlation was 0.716, 0.792 and 0.790 respectively. It may seem counterintuitive at first that morphological features provided by image patches do not improve model performance. Yet, this mirrors the criteria of the grading scheme, where mitotic count is the only unequivocal parameter., Comment: 12 pages, 3 figures

Published
2021

4. Surgical planning, histopathology findings and postoperative outcome in MR-negative extra-temporal epilepsy using intracranial EEG, functional imaging, magnetoencephalography, neuronavigation and intraoperative MRI

Author

Maslarova, Anna, Zhao, Yining, Rösch, Julie, Dörfler, Arnd, Coras, Roland, Blümcke, Ingmar, Lang, Johannes, Schmidt, Manuel, Hamer, Hajo M., Reindl, Caroline, Welte, Tamara M., Rampp, Stefan, Rössler, Karl, Buchfelder, Michael, and Brandner, Sebastian

Published
2023
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10. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

Author

Aichholzer, Martin, Amorim, Isabel, Aparicio, Javier, Aronica, Eleonora, Arzimanoglou, Alexis, Barba, Carmen, Beck, Jürgen, Becker, Albert, Beckervordersandforth, Jan C, Bien, Christian G, Blümcke, Ingmar, Bodi, Istvan, Braun, Kees PJ, Catenoix, Helene, Chassoux, Francine, Chipaux, Mathilde, Cloppenborg, Thomas, Coras, Roland, Cross, J Helen, De Palma, Luca, De Tisi, Jane, Deleo, Francesco, Devaux, Bertrand, Di Gennaro, Giancarlo, Dorfmüller, Georg, Duncan, John S, Elger, Christian, Ernst, Katharina, Esposito, Vincenzo, Feucht, Martha, Gadze, Zeljka Petelin, Garbelli, Rita, Geleijns, Karin, Gil-Nagel, Antonio, Grote, Alexander, Grunwald, Thomas, Guerrini, Renzo, Hamer, Hajo, Honavar, Mrinalini, Jacques, Thomas S, Jakovcevic, Antonia, Jutila, Leena, Kalina, Adam, Kälviäinen, Reetta, Klein, Karl Martin, Koenig, Kristina, Krsek, Pavel, Kudernatsch, Manfred, Kudr, Martin, Lamberink, Herm J, Malmgren, Kristina, Marusic, Petr, Melikyan, Armen, Menzler, Katja, Noachtar, Soheyl, Otte, Willem M, Özkara, Çiğdem, Pieper, Tom, Pimentel, Jose, Raicevic, Savo, Rheims, Sylvain, Ribeiro, Joana, Rosenow, Felix, Rössler, Karl, Rydenhag, Bertil, Sales, Francisco, San Antonio-Arce, Victoria, Schaller, Karl Lothar, Schijns, Olaf, Scholl, Theresa, Schramm, Johannes, Schulze-Bonhage, Andreas, Sciot, Raf, Seeck, Margitta, Shishkina, Lyudmila, Sokic, Dragoslav, Specchio, Nicola, Theys, Tom, Thom, Maria, Delgado, Rafael Toledano, Toulouse, Joseph, Uzan, Mustafa, van Loon, Johannes, Van Paesschen, Wim, von Oertzen, Tim J, Jansen, Floor, Leijten, Frans, van Rijen, Peter, Spliet, Wim GM, Mühlebner, Angelika, Kasper, Burkhard S, Fauser, Susanne, Polster, Tilman, Kalbhenn, Thilo, Delev, Daniel, McEvoy, Andrew, Miserocchi, Anna, Landré, Elisabeth, Turak, Bares, Varlet, Pascale, Ferrand-Sorbets, Sarah, Fohlen, Martine, Bulteau, Christine, Edelvik, Anna, Shah, Mukesch J, Scheiwe, Christian, Delicado, Eva Gutierrez, Tisdall, Martin, Eltze, Christin, Akkol, Serdar, Deniz, Kaancan, Oz, Buge, Holthausen, Hans, Hartlieb, Till, Staudt, Martin, Casciato, Sara, Quarato, Pier P, Giangaspero, Felice, Streichenberger, Nathalie, Guenot, Marc, Isnard, Jean, Valentijn, Antonio, Chang, Amanda, Mullatti, Nandini, Zamecnik, Josef, Zarubova, Jana, Tomasek, Martin, Immonen, Arto, Saarela, Anni, Rauramaa, Tuomas, Lobrinus, Johannes A, Egervari, Kristof, Momjian, Shahan, Harti, Elisabeth, Lohr, Hannah, Kroell, Judith, Vermeulen, Lynn, Cleeren, Evy, Vlasov, Pavel, Kozlova, Antonia, Vorobyev, Alexey, Goeppel, Gudrun, Samueli, Sharon, Czech, Thomas, Hainfellner, Johannes, Puttinger, Gertraud, Schwarz, Gabriele, Stefanits, Harald, Weis, Serge, Spreafico, Roberto, Villani, Flavio, Rossini, Laura, Hermsen, Anke, Knake, Susanne, Nimsky, Christopher, Carl, Barbara, Belohlavkova, Anezka, Benova, Barbora, Bisschop, Jeroen, Colon, Albert, van Kranen-Mastenbroek, Vivianne, Rouhl, Rob PW, Hoogland, Govert, Rumiá, Jordi, Ramírez-Camacho, Alia, Candela-Cantó, Santiago, Ostrowsky-Coste, Karine, Panagiotakaki, Eleni, Montavont, Alexandra, Kosal, Pascale Keo, Gokce-Samar, Zeynep, Milleret, Clara, Buccoliero, Anna M, Giordano, Flavio, Sulentic, Vlatko, Mrak, Goran, Desnica, Andrej, CarfíPavia, Giusy, De Benedictis, Alessandro, Marras, Carlo E, Bascarevic, Vladimir, Vojvodic, Nikola, Ristic, Aleksandar, Rebelo, Olinda, Aledo-Serrano, Angel, Garcia-Morales, Irene, Anciones, Carla, and Braun, Kees P J

Published
2020
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16. Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping

Author

Di Liberto, Giovanni, Pantelyushin, Stanislav, Kreutzfeldt, Mario, Page, Nicolas, Musardo, Stefano, Coras, Roland, Steinbach, Karin, Vincenti, Ilena, Klimek, Bogna, Lingner, Thomas, Salinas, Gabriela, Lin-Marq, Nathalie, Staszewski, Ori, Costa Jordão, Marta Joana, Wagner, Ingrid, Egervari, Kristof, Mack, Matthias, Bellone, Camilla, Blümcke, Ingmar, Prinz, Marco, Pinschewer, Daniel D., and Merkler, Doron

Published
2018
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20. Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

Author

Scharfman, Helen E., Kanner, Andres M., Friedman, Alon, Blümcke, Ingmar, Crocker, Candice E., Cendes, Fernando, Diaz-Arrastia, Ramon, Förstl, Hans, Fenton, André A., Grace, Anthony A., Palop, Jorge, Morrison, Jason, Nehlig, Astrid, Prasad, Asuri, Wilcox, Karen S., Jette, Nathalie, and Pohlmann-Eden, Bernd

Published
2018
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21. Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias

Author

D’Gama, Alissa M., Woodworth, Mollie B., Hossain, Amer A., Bizzotto, Sara, Hatem, Nicole E., LaCoursiere, Christopher M., Najm, Imad, Ying, Zhong, Yang, Edward, Barkovich, A. James, Kwiatkowski, David J., Vinters, Harry V., Madsen, Joseph R., Mathern, Gary W., Blümcke, Ingmar, Poduri, Annapurna, and Walsh, Christopher A.

Published
2017
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25. Epilepsien

Author

Blümcke, Ingmar, Klöppel, Günter, editor, Kreipe, Hans H., editor, Remmele, Wolfgang, editor, Paulus, Werner, editor, and Schröder, J. Michael, editor

Published
2012
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30. Incidence and prevalence of major epilepsy-associated brain lesions

Author

Lopez-Rivera, Javier A. A., Smuk, Victoria, Leu, Costin, Nasr, Gaelle, Vegh, Deborah, Stefanski, Arthur, Perez-Palma, Eduardo, Busch, Robyn, Jehi, Lara, Najm, Imad, Bluemcke, Ingmar, Lal, Dennis, Lopez-Rivera, Javier A. A., Smuk, Victoria, Leu, Costin, Nasr, Gaelle, Vegh, Deborah, Stefanski, Arthur, Perez-Palma, Eduardo, Busch, Robyn, Jehi, Lara, Najm, Imad, Bluemcke, Ingmar, and Lal, Dennis

Abstract

Epilepsy surgery is an effective treatment option for drug-resistant focal epilepsy patients with associ-ated structural brain lesions. However, little epidemiological data are available regarding the number of patients with these lesions. We reviewed data regarding (1) the prevalence and incidence of epilepsy; (2) the proportion of epilepsy patients with focal epilepsy, drug-resistant epilepsy, and drug-resistant focal epilepsies; and (3) the number of epilepsy presurgical evaluations and surgical resections. We also assessed the relative proportion of brain lesions using post-surgical histopathological findings from 541 surgical patients from the Cleveland Clinic and 9,523 patients from a European multi-center cohort. Data were combined to generate surgical candidate incidence and prevalence estimates and the first lesion-specific estimates for hippocampal sclerosis (HS), low-grade epilepsy-associated brain tumors (LEAT), malformations of cortical development (MCD), glial scars, vascular malformations, and encephalitis. The most frequently diagnosed brain lesions were HS (incidence = 2.32 +/- 0.26 in 100,000, prevalence = 19.40 +/- 2.16 in 100,000) for adults and MCD (incidence = 1.15 +/- 0.34 in 100,000, prevalence = 6.52 +/- 1.89 in 100,000) for children. Our estimates can guide patient advocacy groups, clin-icians, researchers, policymakers in education, development of health care strategy, resource allocation, and reimbursement schedules.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Published
2022

37. The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature

Author

Pepi, Chiara, primary, de Palma, Luca, additional, Trivisano, Marina, additional, Pietrafusa, Nicola, additional, Lepri, Francesca Romana, additional, Diociaiuti, Andrea, additional, Camassei, Francesca Diomedi, additional, Carfi-Pavia, Giusy, additional, De Benedictis, Alessandro, additional, Rossi-Espagnet, Camilla, additional, Vigevano, Federico, additional, Marras, Carlo Efisio, additional, Novelli, Antonio, additional, Bluemcke, Ingmar, additional, and Specchio, Nicola, additional

Published
2021
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39. Epilepsy Surgery in the First Months of Life

Author

Borggraefe, Ingo, additional, Bluemcke, Ingmar, additional, Coras, Roland, additional, Noachtar, Soheyl, additional, Vollmar, Christian, additional, Leiz, Steffen, additional, Tacke, Moritz, additional, Heinen, Florian, additional, Kunz, Mathias, additional, and Peraud, Aurelia, additional

Published
2019
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41. A comprehensive clinico-pathological and genetic evaluation of bottom-of-sulcus focal cortical dysplasia in patients with difficult-to-localize focal epilepsy

Author

Ying, Zhong, Wang, Irene, Bluemcke, Ingmar, Bulacio, Juan, Alexopoulos, Andreas, Jehi, Lara, Bingaman, William, Gonzalez-Martinez, Jorge, Kobow, Katja, Niestroj, Lisa Marie, Lal, Dennis, Koelble, Konrad, Najm, Imad, Ying, Zhong, Wang, Irene, Bluemcke, Ingmar, Bulacio, Juan, Alexopoulos, Andreas, Jehi, Lara, Bingaman, William, Gonzalez-Martinez, Jorge, Kobow, Katja, Niestroj, Lisa Marie, Lal, Dennis, Koelble, Konrad, and Najm, Imad

Abstract

Aims. We comprehensively studied the clinical presentation, stereo-EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug-resistant patients with difficult-to-localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS-FCD).Methods. We identified 10 patients with BOS-FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video-EEG monitoring. Brain MRI, including voxel-based morphometric analysis and surgical tissue submitted for histopathology, was reviewed. Paraffin tissue samples from five patients were made available for targeted next-generation sequencing. Postsurgical follow-up was available in nine patients.Results. BOS-FCD was identified in the superior frontal sulcus in six patients, inferior frontal sulcus in one patient, central sulcus in one patient, and intraparietal sulcus in two patients. All patients had stereotyped seizures. Intracranial EEG recordings identified ictal onset at the BOS-FCD in all 10 patients, whereas ictal scalp EEG had a localizing value in only six patients. Complete resection was achieved by lesionectomy or focal corticectomy in nine patients. Histopathologically, six patients had FCD type IIb and three had FCD type IIa. Next-generation sequencing analysis of DNA extracted from lesion-enriched (micro-dissected) tissue from five patients with FCD type II led to the identification of a germline frameshift insertion in DEPDC5, introducing a premature stop in one patient. Eight out of nine patients with available follow-up were completely seizure-free (Engel Class IA) after a mean follow-up period of six years.Conclusion. Our results confirm previous studies classifying difficult-to-localize BOS-FCD into the emerging spectrum of FCD ILAE type II mTORopathies. Further studies with large patient numbers and ultra-deep genetic testing may help to bridge the current knowledge gap in genetic aetiologies of FCD.

Published
2019

42. Assessment of genetic variant burden in epilepsy-associated brain lesions

Author

Niestroj, Lisa-Marie, May, Patrick, Artomov, Mykyta, Kobow, Katja, Coras, Roland, Perez-Palma, Eduardo, Altmueller, Janine, Thiele, Holger, Nuernberg, Peter, Leu, Costin, Palotie, Aarno, Daly, Mark J., Klein, Karl Martin, Beschorner, Rudi, Weber, Yvonne G., Bluemcke, Ingmar, Lal, Dennis, Niestroj, Lisa-Marie, May, Patrick, Artomov, Mykyta, Kobow, Katja, Coras, Roland, Perez-Palma, Eduardo, Altmueller, Janine, Thiele, Holger, Nuernberg, Peter, Leu, Costin, Palotie, Aarno, Daly, Mark J., Klein, Karl Martin, Beschorner, Rudi, Weber, Yvonne G., Bluemcke, Ingmar, and Lal, Dennis

Abstract

It is challenging to estimate genetic variant burden across different subtypes of epilepsy. Herein, we used a comparative approach to assess the genetic variant burden and genotype-phenotype correlations in four most common brain lesions in patients with drug-resistant focal epilepsy. Targeted sequencing analysis was performed for a panel of 161 genes with a mean coverage of >400x. Lesional tissue was histopathologically reviewed and dissected from hippocampal sclerosis (n = 15), ganglioglioma (n = 16), dysembryoplastic neuroepithelial tumors (n = 8), and focal cortical dysplasia type II (n = 15). Peripheral blood (n = 12) or surgical tissue samples histopathologically classified as lesion-free (n = 42) were available for comparison. Variants were classified as pathogenic or likely pathogenic according to American College of Medical Genetics and Genomics guidelines. Overall, we identified pathogenic and likely pathogenic variants in 25.9% of patients with a mean coverage of 383x. The highest number of pathogenic/likely pathogenic variants was observed in patients with ganglioglioma (43.75%; all somatic) and dysembryoplastic neuroepithelial tumors (37.5%; all somatic), and in 20% of cases with focal cortical dysplasia type II (13.33% somatic, 6.67% germline). Pathogenic/likely pathogenic positive genes were disorder specific and BRAF V600E the only recurrent pathogenic variant. This study represents a reference for the genetic variant burden across the four most common lesion entities in patients with drug-resistant focal epilepsy. The observed large variability in variant burden by epileptic lesion type calls for whole exome sequencing of histopathologically well-characterized tissue in a diagnostic setting and in research to discover novel disease-associated genes.

Published
2019

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

Author

Capper, David, Jones, David T. W., 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, Hoelsken, 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, Juergen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brueck, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Haenggi, 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, Muehleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernaiz, Kramm, Christof M., Mueller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Fruehwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Bluemcke, Ingmar, Bendszus, Martin, Debus, Juergen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schueller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, Pfister, Stefan M., Capper, David, Jones, David T. W., 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, Hoelsken, 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, Juergen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brueck, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Haenggi, 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, Muehleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernaiz, Kramm, Christof M., Mueller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Fruehwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Bluemcke, Ingmar, Bendszus, Martin, Debus, Juergen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schueller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, and Pfister, Stefan M.

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 challengingwith 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

46. Guideline-based and bioinformatic reassessment of lesion-associated gene and variant pathogenicity in focal human epilepsies

Author

Niestroj, Lisa-Marie, Du, Juanjiangmeng, Nothnagel, Michael, May, Patrick, Palotie, Aarno, Daly, Mark J., Nuernberg, Peter, Bluemcke, Ingmar, Lal, Dennis, Niestroj, Lisa-Marie, Du, Juanjiangmeng, Nothnagel, Michael, May, Patrick, Palotie, Aarno, Daly, Mark J., Nuernberg, Peter, Bluemcke, Ingmar, and Lal, Dennis

Abstract

Objective Increasing availability of surgically resected brain tissue from patients with focal epilepsy and focal cortical dysplasia or low-grade glioneuronal tumors has fostered large-scale genetic examination. However, assessment of pathogenicity of germ line and somatic variants remains difficult. Here, we present a state-of-the-art evaluation of reported genes and variants associated with epileptic brain lesions. Methods Results We critically reevaluated the pathogenicity for all neuropathology-associated variants reported to date in the PubMed and ClinVar databases, including 101 neuropathology-associated missense variants encompassing 11 disease-related genes. We assessed gene variant tolerance and classified all identified missense variants according to guidelines from the American College of Medical Genetics and Genomics (ACMG). We further extended the bioinformatic variant prediction by introducing a novel gene-specific deleteriousness ranking for prediction scores. Application of ACMG guidelines and in silico gene variant tolerance analysis classified only seven of 11 genes to be likely disease-associated according to the reported disease mechanism, whereas 61 (60.4%) of 101 variants of those genes were classified as of uncertain significance, 37 (36.6%) as being likely pathogenic, and 3 (3%) as being pathogenic. Significance We concluded that the majority of neuropathology-associated variants reported to date do not have enough evidence to be classified as pathogenic. Interpretation of lesion-associated variants remains challenging, and application of current ACMG guidelines is recommended for interpretation and prediction.

Published
2018

50. VCP and PSMF1: Antagonistic regulators of proteasome activity

Author

Clemen, Christoph S., Marko, Marija, Strucksberg, Karl-Heinz, Behrens, Juliane, Wittig, Ilka, Gärtner, Linda, Winter, Lilli, Chevessier, Frederic, Matthias, Jan, Türk, Matthias, Tangavelou, Karthikeyan, Schütz, Johanna, Arhzaouy, Khalid, Klopffleisch, Karsten, Hanisch, Franz-Georg, Rottbauer, Wolfgang, Blümcke, Ingmar, Just, Steffen, Eichinger, Ludwig, Hofmann, Andreas, and Schröder, Rolf

Published
2015
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