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38 results on '"Hench, Juergen"'

1. DNA Methylation Profiling of Salivary Gland Tumors Supports and Expands Conventional Classification

Author

Jurmeister, Philipp, Leitheiser, Maximilian, Arnold, Alexander, Capilla, Emma Payá, Mochmann, Liliana H., Zhdanovic, Yauheniya, Schleich, Konstanze, Jung, Nina, Chimal, Edgar Calderon, Jung, Andreas, Kumbrink, Jörg, Harter, Patrick, Prenißl, Niklas, Elezkurtaj, Sefer, Brcic, Luka, Deigendesch, Nikolaus, Frank, Stephan, Hench, Jürgen, Försch, Sebastian, Breimer, Gerben, van Engen van Grunsven, Ilse, Lassche, Gerben, van Herpen, Carla, Zhou, Fang, Snuderl, Matija, Agaimy, Abbas, Müller, Klaus-Robert, von Deimling, Andreas, Capper, David, Klauschen, Frederick, and Ihrler, Stephan

Published
2024
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2. Zentrales Nervensystem

Author

Winkler, David, Mariani, Luigi, Cordier, Dominik, Guzman, Raphael, Marchis, Gian Marco De, Hench, Jürgen, Frank, Stephan, Karlin, Kirill, Cerny, Thomas, Cerny, Thomas, editor, and Karlin, Kirill, editor

Published
2023
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3. Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth

Author

Della Monica, Rosa, Buonaiuto, Michela, Cuomo, Mariella, Pagano, Cristina, Trio, Federica, Costabile, Davide, de Riso, Giulia, Cicala, Francesca Sveva, Raia, Maddalena, Franca, Raduan Ahmed, Del Basso De Caro, Marialaura, Sorrentino, Domenico, Navarra, Giovanna, Coppola, Laura, Tripodi, Lorella, Pastore, Lucio, Hench, Juergen, Frank, Stephan, Schonauer, Claudio, Catapano, Giuseppe, Bifulco, Maurizio, Chiariotti, Lorenzo, and Visconti, Roberta

Published
2023
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4. Clinical, histopathological and molecular features of dedifferentiated melanomas: An EORTC Melanoma Group Retrospective Analysis

Author

Hench, Juergen, Mihic-Probst, Daniela, Agaimy, Abbas, Frank, Stephan, Meyer, Peter, Hultschig, Claus, Simi, Sara, Alos, Lucia, Balamurugan, Thiagarajah, Blokx, Willeke, Bosisio, Francesca, Cappellesso, Rocco, Griewank, Klaus, Hadaschik, Eva, van Kempen, Leon C., Kempf, Werner, Lentini, Maria, Mazzucchelli, Luca, Rinaldi, Gaetana, Rutkowski, Piotr, Schadendorf, Dirk, Schilling, Bastian, Szumera-Cieckiewicz, Anna, van den Oord, Joost, Mandalà, Mario, and Massi, Daniela

Published
2023
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7. Zentrales Nervensystem

Author

Winkler, David, Mariani, Luigi, Cordier, Dominik, Guzman, Raphael, Marco De Marchis, Gian, Hench, Jürgen, Frank, Stephan, Cerny, Thomas, editor, and Karlin, Kirill, editor

Published
2019
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9. Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features

Author

Haefliger, Simon, Hench, Juergen, O'Rourke, Colm J., Meyer-Schaller, Nathalie, Uzun, Sarp, Saldarriaga, Joan, Weber, Achim, Mazzucchelli, Luca, Jermann, Philip, Frank, Stephan, Andersen, Jesper B., Terracciano, Luigi, Sempoux, Christine, Matter, Matthias S., Haefliger, Simon, Hench, Juergen, O'Rourke, Colm J., Meyer-Schaller, Nathalie, Uzun, Sarp, Saldarriaga, Joan, Weber, Achim, Mazzucchelli, Luca, Jermann, Philip, Frank, Stephan, Andersen, Jesper B., Terracciano, Luigi, Sempoux, Christine, and Matter, Matthias S.

Abstract

BackgroundHepatocellular adenoma (HCA) is a rare liver tumour, which can have atypical morphological features such as cytological atypia, pseudoglandular architecture, and altered reticulin framework. Little is known about the genetic and epigenetic alterations of such HCAs and whether they show the alterations classically found in hepatocellular carcinoma (HCC) or in HCA without atypical morphology. MethodsWe analysed five HCAs with atypical morphological features and one HCA with transition to HCC. Every tumour was subtyped by immunohistochemistry, sequenced by a targeted NGS panel, and analysed on a DNA methylation microarray. ResultsSubtyping of the five HCAs with atypical features revealed two beta-catenin mutated HCA (b-HCA), two beta-catenin mutated inflammatory HCA (b-IHCA), and one sonic hedgehog activated HCA (shHCA). None of them showed mutations typically found in HCC, such as, e.g. TERT or TP53 mutations. The epigenomic pattern of HCAs with atypical morphological features clustered with reference data for HCAs without atypical morphological features but not with HCC. Similarly, phyloepigenetic trees using the DNA methylation data reproducibly showed that HCAs with morphological atypia are much more similar to nonmalignant samples than to malignant samples. Finally, atypical HCAs showed no relevant copy number variations (CNV). ConclusionIn our series, mutational, DNA methylation, as well as CNV analyses, supported a relationship of atypical HCAs with nonatypical HCAs rather than with HCC. Therefore, in cases with difficult differential diagnosis between HCC and HCA, it might be advisable to perform targeted sequencing and/or combined methylation/copy number profiling.

Published
2023

11. Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features

Author

Haefliger, Simon, primary, Hench, Juergen, additional, O'Rourke, Colm J, additional, Meyer‐Schaller, Nathalie, additional, Uzun, Sarp, additional, Saldarriaga, Joan, additional, Weber, Achim, additional, Mazzucchelli, Luca, additional, Jermann, Philip, additional, Frank, Stephan, additional, Andersen, Jesper B, additional, Terracciano, Luigi, additional, Sempoux, Christine, additional, and Matter, Matthias S, additional

Published
2023
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12. Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms [*Della Monica, R. e Cuomo, M. co-primi autori]

Author

Della Monica, Rosa, Cuomo, Mariella, Visconti, Roberta, di Mauro, Annabella, Buonaiuto, Michela, Costabile, Davide, De Riso, Giulia, Di Risi, Teodolinda, Guadagno, Elia, Tafuto, Roberto, Lamia, Sabrina, Ottaiano, Alessandro, Cappabianca, Paolo, Del Basso de Caro, Maria Laura, Tatangelo, Fabiana, Hench, Juergen, Frank, Stephan, Tafuto, Salvatore, Chiariotti, Lorenzo, Della Monica, Rosa, Cuomo, Mariella, Visconti, Roberta, di Mauro, Annabella, Buonaiuto, Michela, Costabile, Davide, De Riso, Giulia, Di Risi, Teodolinda, Guadagno, Elia, Tafuto, Roberto, Lamia, Sabrina, Ottaiano, Alessandro, Cappabianca, Paolo, Del Basso de Caro, Maria Laura, Tatangelo, Fabiana, Hench, Juergen, Frank, Stephan, Tafuto, Salvatore, and Chiariotti, Lorenzo

Abstract

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.

Published
2022

14. PATH-04. Array-based global DNA Methylation profiling of mouse brain tumors allows comparison to human tumors

Author

Schoof, Melanie, primary, Spohn, Michael, additional, Dorostkar, Mario, additional, Neyazi, Sina, additional, Bockmayr, Michael, additional, Swartling, Fredrik, additional, Kawauchi, Daisuke, additional, Gilbertson, Richard, additional, Taylor, Jessica, additional, Pei, Yanxin, additional, Glass, Rainer, additional, Cheng, Jiying, additional, Galarza, Natalia Moreno, additional, Hench, Juergen, additional, Herms, Jochen, additional, Jurmeister, Philipp, additional, Schweizer, Leonille, additional, Capper, David, additional, Harter, Patrick, additional, Thomas, Christian, additional, Hasselblatt, Martin, additional, Blattner-Johnson, Mirjam, additional, Jones, David, additional, Frank, Stephan, additional, Kerl, Kornelius, additional, and Schüller, Ulrich, additional

Published
2022
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17. Integrated Analysis Of Immunotherapy Treated Clear Cell Renal Cell Carcinomas: An Exploratory Study

Author

Sobottka-Brillout, Bettina, Nienhold, Ronny, Nowak, Marta, Hench, Juergen, Haeuptle, Pirmin, Frank, Angela, Sachs, Melanie, Kahraman, Abdullah; https://orcid.org/0000-0003-3523-4467, Moch, Holger; https://orcid.org/0000-0002-7986-2839, Koelzer, Viktor H; https://orcid.org/0000-0001-9206-4885, Mertz, Kirsten D; https://orcid.org/0000-0002-3074-6925, Sobottka-Brillout, Bettina, Nienhold, Ronny, Nowak, Marta, Hench, Juergen, Haeuptle, Pirmin, Frank, Angela, Sachs, Melanie, Kahraman, Abdullah; https://orcid.org/0000-0003-3523-4467, Moch, Holger; https://orcid.org/0000-0002-7986-2839, Koelzer, Viktor H; https://orcid.org/0000-0001-9206-4885, and Mertz, Kirsten D; https://orcid.org/0000-0002-3074-6925

Abstract

Molecular or immunological differences between responders and nonresponders to immune checkpoint inhibitors (ICIs) of clear cell renal cell carcinomas (ccRCCs) remain incompletely understood. To address this question, we performed next-generation sequencing, methylation analysis, genome wide copy number analysis, targeted RNA sequencing and T-cell receptor sequencing, and we studied frequencies of tumor-infiltrating CD8+ T cells, presence of tertiary lymphoid structures (TLS) and PD-L1 expression in 8 treatment-naive ccRCC patients subsequently treated with ICI (3 responders, 5 nonresponders). Unexpectedly, we identified decreased frequencies of CD8+ tumor-infiltrating T cells and TLS, and a decreased expression of PD-L1 in ICI responders when compared with nonresponders. However, neither tumor-specific genetic alterations nor gene expression profiles correlated with response to ICI or the observed immune features. Our results underline the challenge to stratify ccRCC patients for immunotherapy based on routinely available pathologic primary tumor material, even with advanced technologies. Our findings emphasize the analysis of pretreated metastatic tissue in line with recent observations describing treatment effects on the tumor microenvironment. In addition, our data call for further investigation of additional parameters in a larger ccRCC cohort to understand the mechanistic implications of the observed differences in tumor-infiltrating CD8+ T cells, TLS, and PD-L1 expression.

Published
2022

18. Anti-GABAA receptor encephalitis 14 months after allogeneic haematopoietic stem-cell transplant for acute myeloid leukaemia

Author

Rusche, Thilo, Yaldizli, Özgür, Galbusera, Riccardo, Mutke, Matthias, Halter, Jörg P, Lieb, Johanna, Matteazzi, Francesca, Stelmes, Anne, Bittner, Jan, Grzonka, Pascale, Frank, Nicole, Cordier, Dominik, Hench, Jürgen, Frank, Stephan, Hirsch, Hans H, Fischer, Urs, Kuhle, Jens, Sutter, Raoul, Rüegg, Stephan, and Fisch, Urs

Published
2024
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20. Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms

Author

Della Monica, Rosa, primary, Cuomo, Mariella, additional, Visconti, Roberta, additional, di Mauro, Annabella, additional, Buonaiuto, Michela, additional, Costabile, Davide, additional, De Riso, Giulia, additional, Di Risi, Teodolinda, additional, Guadagno, Elia, additional, Tafuto, Roberto, additional, Lamia, Sabrina, additional, Ottaiano, Alessandro, additional, Cappabianca, Paolo, additional, Del Basso de Caro, Maria Laura, additional, Tatangelo, Fabiana, additional, Hench, Juergen, additional, Frank, Stephan, additional, Tafuto, Salvatore, additional, and Chiariotti, Lorenzo, additional

Published
2021
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23. Supratentorial ependymoma in childhood: more than just RELA or YAP

Author

Zschernack, Valentina, Junger, Stephanie T., Mynarek, Martin, Rutkowski, Stefan, Garre, Maria Luisa, Ebinger, Martin, Neu, Marie, Faber, Joerg, Erdlenbruch, Bernhard, Claviez, Alexander, Bielack, Stefan, Brozou, Triantafyllia, Fruehwald, Michael C., Doerner, Evelyn, Dreschmann, Verena, Stock, Annika, Solymosi, Laszlo, Hench, Juergen, Frank, Stephan, Vokuhl, Christian, Waha, Andreas, Andreiuolo, Felipe, Pietsch, Torsten, Zschernack, Valentina, Junger, Stephanie T., Mynarek, Martin, Rutkowski, Stefan, Garre, Maria Luisa, Ebinger, Martin, Neu, Marie, Faber, Joerg, Erdlenbruch, Bernhard, Claviez, Alexander, Bielack, Stefan, Brozou, Triantafyllia, Fruehwald, Michael C., Doerner, Evelyn, Dreschmann, Verena, Stock, Annika, Solymosi, Laszlo, Hench, Juergen, Frank, Stephan, Vokuhl, Christian, Waha, Andreas, Andreiuolo, Felipe, and Pietsch, Torsten

Abstract

Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a YAP-MAMLD1 fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-RELA/non-YAP supratentorial ependymomas that were systematically characterized by means of their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis of fusion transcripts by Nanostring technology, and RNA sequencing. Based upon histological and immunohistochemical features two main patterns were identified-RELA-like (n = 9) and tanycytic ependymomas (n = 6). In the RELA-like group histologically assigned to WHO grade III and resembling RELA-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-kappa B pathway. Three tumors showed alternative C11orf95 fusions to MAML2 or NCOA1. A methylation-based brain tumor classifier assigned two RELA-like tumors to the methylation class EP, RELA-fusion; the others demonstrated no significant similarity score. Of the tanycytic group, 5/6 tumors were assigned a WHO grade II. No gene fusions were detected. Methylation profiling did not show any association with an established methylation class. We additionally identified two astroblastoma-like tumors that both presented with chromothripsis of chromosome 22 but lacked MN1 breaks according to FISH analysis. They revealed novel fusion events involving genes in chromosome 22. One further tumor with polyploid cytogenetics was interpreted as PFB ependymoma by the brain tumor methylation classifier but had no relation to the posterior fossa. Clinical follow-up was available for 16/18 patients. Patients with tanycytic and astroblastoma-like tumors had no relapse, while 2 patie

Published
2021

24. Sarcoma classification by DNA methylation profiling

Author

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

Abstract

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications. Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Published
2021

25. Differentiation of rare brain tumors through unsupervised machine learning: Clinical significance of in-depth methylation and copy number profiling illustrated through an unusual case of IDH wildtype glioblastoma

Author

Saleh, Christian, primary, Jaszczuk, Phillip, additional, Hund-Georgiadis, Margret, additional, Frank, Stephan, additional, Cordier, Dominik, additional, Hench, Ivana Bratic, additional, Todea, Alexandra, additional, Wasilewski, Andrea, additional, Wilmes, Stefanie, additional, Grigioni, Giulia, additional, and Hench, Juergen, additional

Published
2021
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27. 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

28. Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms.

Author

Monica, Rosa Della, Cuomo, Mariella, Visconti, Roberta, Mauro, Annabella di, Buonaiuto, Michela, Costabile, Davide, De Riso, Giulia, Risi, Teodolinda Di, Guadagno, Elia, Tafuto, Roberto, Lamia, Sabrina, Ottaiano, Alessandro, Cappabianca, Paolo, Del Basso de Caro, Maria Laura, Tatangelo, Fabiana, Hench, Juergen, Frank, Stephan, Tafuto, Salvatore, and Chiariotti, Lorenzo

Subjects
NEUROENDOCRINE tumors, O6-Methylguanine-DNA Methyltransferase, ALKYLATING agents, METHYLATION, BRAIN tumors
Abstract

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs. [ABSTRACT FROM AUTHOR]

Published
2020
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32. Granulomatous encephalitis: protothecosis excluded?

Author

Hench, Juergen, primary, Roschanski, Nicole, additional, Hewer, Ekkehard, additional, Rösler, Uwe, additional, Lass‐Flörl, Cornelia, additional, Stippich, Christoph, additional, Tolnay, Markus, additional, Rusche, Norman, additional, Sonderegger, Beat, additional, Sailer, Martin, additional, Lyrer, Philippe, additional, Peters, Nils, additional, and Frank, Stephan, additional

Published
2016
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34. A Tissue-Specific Approach to the Analysis of Metabolic Changes in Caenorhabditis elegans

Author

Hench, Juergen, Hench, Ivana Bratic, Pujol, Claire, Ipsen, Sabine, Brodesser, Susanne, Mourier, Arnaud, Tolnay, Markus, Frank, Stephan, Trifunovic, Aleksandra, Hench, Juergen, Hench, Ivana Bratic, Pujol, Claire, Ipsen, Sabine, Brodesser, Susanne, Mourier, Arnaud, Tolnay, Markus, Frank, Stephan, and Trifunovic, Aleksandra

Abstract

The majority of metabolic principles are evolutionarily conserved from nematodes to humans. Caenorhabditis elegans has widely accelerated the discovery of new genes important to maintain organismic metabolic homeostasis. Various methods exist to assess the metabolic state in worms, yet they often require large animal numbers and tend to be performed as bulk analyses of whole worm homogenates, thereby largely precluding a detailed studies of metabolic changes in specific worm tissues. Here, we have adapted well-established histochemical methods for the use on C. elegans fresh frozen sections and demonstrate their validity for analyses of morphological and metabolic changes on tissue level in wild type and various mutant strains. We show how the worm presents on hematoxylin and eosin (H&E) stained sections and demonstrate their usefulness in monitoring and the identification of morphological abnormalities. In addition, we demonstrate how Oil-Red-O staining on frozen worm cross-sections permits quantification of lipid storage, avoiding the artifact-prone fixation and permeabilization procedures of traditional whole-mount protocols. We also adjusted standard enzymatic stains for respiratory chain subunits (NADH, SDH, and COX) to monitor metabolic states of various C. elegans tissues. In summary, the protocols presented here provide technical guidance to obtain robust, reproducible and quantifiable tissue-specific data on worm morphology as well as carbohydrate, lipid and mitochondrial energy metabolism that cannot be obtained through traditional biochemical bulk analyses of worm homogenates. Furthermore, analysis of worm cross-sections overcomes the common problem with quantification in three-dimensional whole-mount specimens.

Published
2011

38. Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms.

Author

Della Monica R, Cuomo M, Visconti R, di Mauro A, Buonaiuto M, Costabile D, De Riso G, Di Risi T, Guadagno E, Tafuto R, Lamia S, Ottaiano A, Cappabianca P, Del Basso de Caro ML, Tatangelo F, Hench J, Frank S, Tafuto S, and Chiariotti L

Subjects
DNA Methylation, DNA Modification Methylases genetics, DNA Repair Enzymes genetics, Humans, Promoter Regions, Genetic, Temozolomide, Tumor Suppressor Proteins genetics, Antineoplastic Agents, Alkylating, Brain Neoplasms genetics
Abstract

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.

Published
2022
Full Text
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