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273 results on '"Nagel, Inga"'

4. UBTF::ATXN7L3 gene fusion defines novel B cell precursor ALL subtype with CDX2 expression and need for intensified treatment

Author

Bastian, Lorenz, Hartmann, Alina M., Beder, Thomas, Hänzelmann, Sonja, Kässens, Jan, Bultmann, Miriam, Hoeppner, Marc P., Franzenburg, Sören, Wittig, Michael, Franke, Andre, Nagel, Inga, Spielmann, Malte, Reimer, Niklas, Busch, Hauke, Schwartz, Stefan, Steffen, Björn, Viardot, Andreas, Döhner, Konstanze, Kondakci, Mustafa, Wulf, Gerald, Wendelin, Knut, Renzelmann, Andrea, Kiani, Alexander, Trautmann, Heiko, Neumann, Martin, Gökbuget, Nicola, Brüggemann, Monika, and Baldus, Claudia D.

Published
2022
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6. Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features

Author

Aukema, Sietse M., Croci, Giorgio A., Bens, Susanne, Oehl-Huber, Kathrin, Wagener, Rabea, Ott, German, Rosenwald, Andreas, Kluin, Philip M., van den Berg, Eva, Bosga-Bouwer, Anneke G., Hoogendoorn, Mels, Hoster, Eva, Bittmann, Iris, Nagel, Inga, Murga Penas, Eva M., Kreuz, Markus, Bausinger, Julia, Belder, Wilfried, Oschlies, Ilske, Dyer, Martin J. S., Jayne, Sandrine, Siebert, Reiner, and Klapper, Wolfram

Published
2021
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7. CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum

Author

Konrad, Enrico D.H., Nardini, Niels, Caliebe, Almuth, Nagel, Inga, Young, Dana, Horvath, Gabriella, Santoro, Stephanie L., Shuss, Christine, Ziegler, Alban, Bonneau, Dominique, Kempers, Marlies, Pfundt, Rolph, Legius, Eric, Bouman, Arjan, Stuurman, Kyra E., Õunap, Katrin, Pajusalu, Sander, Wojcik, Monica H., Vasileiou, Georgia, Le Guyader, Gwenaël, Schnelle, Hege M., Berland, Siren, Zonneveld-Huijssoon, Evelien, Kersten, Simone, Gupta, Aditi, Blackburn, Patrick R., Ellingson, Marissa S., Ferber, Matthew J., Dhamija, Radhika, Klee, Eric W., McEntagart, Meriel, Lichtenbelt, Klaske D., Kenney, Amy, Vergano, Samantha A., Abou Jamra, Rami, Platzer, Konrad, Ella Pierpont, Mary, Khattar, Divya, Hopkin, Robert J., Martin, Richard J., Jongmans, Marjolijn C.J., Chang, Vivian Y., Martinez-Agosto, Julian A., Kuismin, Outi, Kurki, Mitja I., Pietiläinen, Olli, Palotie, Aarno, Maarup, Timothy J., Johnson, Diana S., Venborg Pedersen, Katja, Laulund, Lone W., Lynch, Sally A., Blyth, Moira, Prescott, Katrina, Canham, Natalie, Ibitoye, Rita, Brilstra, Eva H., Shinawi, Marwan, Fassi, Emily, Sticht, Heinrich, Gregor, Anne, Van Esch, Hilde, and Zweier, Christiane

Published
2019
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11. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study

Author

Copie-Bergman, Christiane, Cuillière-Dartigues, Peggy, Baia, Maryse, Briere, Josette, Delarue, Richard, Canioni, Danielle, Salles, Gilles, Parrens, Marie, Belhadj, Karim, Fabiani, Bettina, Recher, Christian, Petrella, Tony, Ketterer, Nicolas, Peyrade, Frederic, Haioun, Corinne, Nagel, Inga, Siebert, Reiner, Jardin, Fabrice, Leroy, Karen, Jais, Jean-Philippe, Tilly, Herve, Molina, Thierry Jo, and Gaulard, Philippe

Published
2015
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13. A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma

Author

Salaverria, Itziar, Martin-Guerrero, Idoia, Wagener, Rabea, Kreuz, Markus, Kohler, Christian W., Richter, Julia, Pienkowska-Grela, Barbara, Adam, Patrick, Burkhardt, Birgit, Claviez, Alexander, Damm-Welk, Christine, Drexler, Hans G., Hummel, Michael, Jaffe, Elaine S., Küppers, Ralf, Lefebvre, Christine, Lisfeld, Jasmin, Löffler, Markus, Macleod, Roderick A.F., Nagel, Inga, Oschlies, Ilske, Rosolowski, Maciej, Russell, Robert B., Rymkiewicz, Grzegorz, Schindler, Detlev, Schlesner, Matthias, Scholtysik, René, Schwaenen, Carsten, Spang, Rainer, Szczepanowski, Monika, Trümper, Lorenz, Vater, Inga, Wessendorf, Swen, Klapper, Wolfram, and Siebert, Reiner

Published
2014
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17. The genomic and transcriptional landscape of primary central nervous system lymphoma

Author

Radke, Josefine, Ishaque, Naveed, Hostench, Xavier Pastor, Richter, Julia, Rosenstiel, Philip, Rosenwald, Andreas, Schilhabel, Markus, Schreiber, Stefanie, Vater, Inga, Wagener, Rabea, Siebert, Reiner, Bernhart, Stephan H, Binder, Hans, Borgoni, Simone, Doose, Gero, Eils, Roland, Hoffmann, Steve, Hopp, Lydia, Kleinheinz, Kortine, Kretzmer, Helene, Kreuz, Markus, Korbel, Jan, Langenberger, David, Loeffler, Markus, Juraeva, Dilafruz, Rosolowski, Maciej, Stadler, Peter F, Sungalee, Stephanie, Pritsch, Fabienne, Paramasivam, Nagarajan, Balasubramanian, Gnana Prakash, Schlesner, Matthias, Sahay, Shashwat, Weniger, Marc, Pehl, Debora, Koll, Randi, Radbruch, Helena, Osterloh, Anja, Korfel, Agnieszka, Misch, Martin, Onken, Julia, Faust, Katharina, Vajkoczy, Peter, Moskopp, Dag, Wang, Yawen, Jödicke, Andreas, Gu, Zuguang, Trümper, Lorenz, Anagnostopoulos, Ioannis, Lenze, Dido, Küppers, Ralf, Hummel, Michael, Schmitt, Clemens A, Wiestler, Otmar D, Wolf, Stephan, Unterberg, Andreas, Schumann, Elisa, Herold-Mende, Christel, Brors, Benedikt, Consortium, ICGC MMML-Seq, Wiemann, Stefan, Heppner, Frank, Wagner, Susanne, Haake, Andrea, Sieverling, Lina, Richter, Gesine, Lawerenz, Chris, Eils, Jürgen, Kerssemakers, Jules, Jaeger-Schmidt, Christina, Scholz, Ingrid, Bergmann, Anke K, Borst, Christoph, Braulke, Friederike, Uhrig, Sebastian, Burkhardt, Birgit, Claviez, Alexander, Dreyling, Martin, Eberth, Sonja, Einsele, Hermann, Frickhofen, Norbert, Haas, Siegfried, Hansmann, Martin-Leo, Karsch, Dennis, Klepl, Nicole, Hübschmann, Daniel, Kneba, Michael, Lisfeld, Jasmin, Mantovani-Löffler, Luisa, Rohde, Marius, Ott, German, Stadler, Christina, Staib, Peter, Stilgenbauer, Stephan, Zenz, Thorsten, Toprak, Umut H, Kube, Dieter, Klapper, Wolfram, Kostezka, Ulrike, Möller, Peter, Szczepanowski, Monika, Ammerpohl, Ole, Aukema, Sietse M, López, Cristina, Binder, Vera, Borkhardt, Arndt, Hoell, Jessica I, Leich, Ellen, Lichter, Peter, Nagel, Inga, Pischimariov, Jordan, Radlwimmer, Bernhard, Weniger, Marc (Beitragende*r), and Küppers, Ralf (Beitragende*r)

Subjects
Central Nervous System, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Cancer Research, Multidisciplinary, genetics [Central Nervous System Neoplasms], Medizin, General Physics and Astronomy, pathology [Central Nervous System Neoplasms], Genomics, General Chemistry, metabolism [Lymphoma, Large B-Cell, Diffuse], General Biochemistry, Genetics and Molecular Biology, Central Nervous System Neoplasms, hemic and lymphatic diseases, metabolism [Central Nervous System], Humans, ddc:610, Lymphoma, Large B-Cell, Diffuse, ddc:500
Abstract

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations.

Published
2022
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19. Clonal evolution in tyrosine kinase inhibitor-resistance: lessons from in vitro-models.

Author

Kaehler, Meike, Osteresch, Pia, Künstner, Axel, Vieth, Stella Juliane, Esser, Daniela, Möller, Marius, Busch, Hauke, Vater, Inga, Spielmann, Malte, Cascorbi, Ingolf, and Nagel, Inga

Subjects
NILOTINIB, PROTEIN-tyrosine kinases, CHRONIC myeloid leukemia, PROTEIN-tyrosine kinase inhibitors, HEMATOLOGIC malignancies, IMATINIB
Abstract

Introduction: Resistance in anti-cancer treatment is a result of clonal evolution and clonal selection. In chronic myeloid leukemia (CML), the hematopoietic neoplasm is predominantly caused by the formation of the BCR::ABL1 kinase. Evidently, treatment with tyrosine kinase inhibitors (TKIs) is tremendously successful. It has become the role model of targeted therapy. However, therapy resistance to TKIs leads to loss of molecular remission in about 25% of CML patients being partially due to BCR::ABL1 kinase mutations, while for the remaining cases, various other mechanisms are discussed. Methods: Here, we established an in vitro-TKI resistance model against the TKIs imatinib and nilotinib and performed exome sequencing. Results: In this model, acquired sequence variants in NRAS, KRAS, PTPN11, and PDGFRB were identified in TKI resistance. The well-known pathogenic NRAS p.(Gln61Lys) variant provided a strong benefit for CML cells under TKI exposure visible by increased cell number (6.2-fold, p < 0.001) and decreased apoptosis (-25%, p < 0.001), proving the functionality of our approach. The transfection of PTPN11 p.(Tyr279Cys) led to increased cell number (1.7-fold, p = 0.03) and proliferation (2.0-fold, p < 0.001) under imatinib treatment. Discussion: Our data demonstrate that our in vitro-model can be used to study the effect of specific variants on TKI resistance and to identify new driver mutations and genes playing a role in TKI resistance. The established pipeline can be used to study candidates acquired in TKI-resistant patients, thereby providing new options for the development of new therapy strategies to overcome resistance. [ABSTRACT FROM AUTHOR]

Published
2023
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22. SMARCA4-mutated atypical teratoid/rhabdoid tumors are associated with inherited germline alterations and poor prognosis

Author

Hasselblatt, Martin, Nagel, Inga, Oyen, Florian, Bartelheim, Kerstin, Russell, Robert B., Schüller, Ulrich, Junckerstorff, Reimar, Rosenblum, Marc, Alassiri, Ali H., Rossi, Sabrina, Schmid, Irene, Gottardo, Nicholas G., Toledano, Helen, Viscardi, Elisabetta, Balbin, Milagros, Witkowski, Leora, Lu, Qianhao, Betts, Matthew J., Foulkes, William D., Siebert, Reiner, Frühwald, Michael C., and Schneppenheim, Reinhard

Published
2014
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25. The landscape of genomic alterations across childhood cancers

Author

Grbner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Hbschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jrgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Gnther H., Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, Lichter, Peter, Weber, Ursula, Eils, Roland, Korshunov, Andrey, Witt, Olaf, Pfister, Stefan, Reifenberger, Guido, Felsberg, Jrg, von Kalle, Christof, Schmidt, Manfred, Bartholom, Cynthia, Taylor, Michael, Jones, David, Jger, Natalie, Korbel, Jan, Sttz, Adrian, Rausch, Tobias, Radlwimmer, Bernhard, Yaspo, Marie-Laure, Lehrach, Hans, Warnatz, Hans-Jrg, Landgraf, Pablo, Brors, Benedikt, Zapatka, Marc, Wagner, Susanne, Haake, Andrea, Richter, Julia, Richter, Gesine, Lawerenz, Chris, Kerssemakers, Jules, Jaeger-Schmidt, Christina, Scholz, Ingrid, Bergmann, Anke K., Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Dreyling, Martin, Eberth, Sonja, Einsele, Hermann, Frickhofen, Norbert, Haas, Siegfried, Hansmann, Martin-Leo, Karsch, Dennis, Kneba, Michael, Lisfeld, Jasmin, Mantovani-Lffler, Luisa, Rohde, Marius, Ott, German, Stadler, Christina, Staib, Peter, Stilgenbauer, Stephan, Trmper, Lorenz, Zenz, Thorsten, Kube, Dieter, Kppers, Ralf, Weniger, Marc, Hummel, Michael, Klapper, Wolfram, Kostezka, Ulrike, Lenze, Dido, Mller, Peter, Rosenwald, Andreas, Szczepanowski, Monika, Ammerpohl, Ole, Aukema, Sietse M., Binder, Vera, Hoell, Jessica I., Leich, Ellen, Lpez, Cristina, Nagel, Inga, Pischimariov, Jordan, Rosenstiel, Philip, Schilhabel, Markus, Schreiber, Stefan, Vater, Inga, Wagener, Rabea, Bernhart, Stephan H., Binder, Hans, Doose, Gero, Hoffmann, Steve, Hopp, Lydia, Kretzmer, Helene, Kreuz, Markus, Langenberger, David, Loeffler, Markus, Rosolowski, Maciej, Schlesner, Matthias, Stadler, Peter F., Sungalee, Stephanie, Kratz, Christian P., van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Frhwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Jones, David T. W., Chavez, Lukas, and Pfister, Stefan M.

Subjects
Childhood cancer -- Genetic aspects, Cancer research, Gene mutation -- Health aspects, Genomics -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 78% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials., Author(s): Susanne N. Grbner [1, 2, 3]; Barbara C. Worst [1, 2, 3, 4]; Joachim Weischenfeldt [5, 6]; Ivo Buchhalter [7]; Kortine Kleinheinz [7]; Vasilisa A. Rudneva [5, 8]; Pascal [...]

Published
2018
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28. Sequential karyotyping in Burkitt lymphoma reveals a linear clonal evolution with increase in karyotype complexity and a high frequency of recurrent secondary aberrations

Author

Aukema, Sietse M., Theil, Laura, Rohde, Marius, Bauer, Benedikt, Bradtke, Jutta, Burkhardt, Birgit, Bonn, Bettina R., Claviez, Alexander, Gattenlöhner, Stefan, Makarova, Olga, Nagel, Inga, Oschlies, Ilske, Pott, Christiane, Szczepanowski, Monika, Traulsen, Arne, Kluin, Philip M., Klapper, Wolfram, Siebert, Reiner, and Murga Penas, Eva M.

Published
2015
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31. Position effects at the FGF8 locus are associated with femoral hypoplasia

Author

Polish National Agency for Academic Exchange, Generalitat de Catalunya, European Commission, National Science Centre (Poland), German Research Foundation, Max Planck Society, Socha, Magdalena, Sowińska-Seidler, Anna, Souto Melo, Uirá, Kragesteen, Bjørt K., Franke, Martin, Heinrich, Verena, Schöpflin, Robert, Nagel, Inga, Gruchy, Nicolas, Mundlos, Stefan, Sreenivasan, Varun K.A., López, Cristina E., Vingron, Martin, Bukowska-Olech, Ewelina, Spielmann, Malte, Jamsheer, Aleksander, Polish National Agency for Academic Exchange, Generalitat de Catalunya, European Commission, National Science Centre (Poland), German Research Foundation, Max Planck Society, Socha, Magdalena, Sowińska-Seidler, Anna, Souto Melo, Uirá, Kragesteen, Bjørt K., Franke, Martin, Heinrich, Verena, Schöpflin, Robert, Nagel, Inga, Gruchy, Nicolas, Mundlos, Stefan, Sreenivasan, Varun K.A., López, Cristina E., Vingron, Martin, Bukowska-Olech, Ewelina, Spielmann, Malte, and Jamsheer, Aleksander

Abstract

Copy-number variations (CNVs) are a common cause of congenital limb malformations and are interpreted primarily on the basis of their effect on gene dosage. However, recent studies show that CNVs also influence the 3D genome chromatin organization. The functional interpretation of whether a phenotype is the result of gene dosage or a regulatory position effect remains challenging. Here, we report on two unrelated families with individuals affected by bilateral hypoplasia of the femoral bones, both harboring de novo duplications on chromosome 10q24.32. The ∼0.5 Mb duplications include FGF8, a key regulator of limb development and several limb enhancer elements. To functionally characterize these variants, we analyzed the local chromatin architecture in the affected individuals’ cells and re-engineered the duplications in mice by using CRISPR-Cas9 genome editing. We found that the duplications were associated with ectopic chromatin contacts and increased FGF8 expression. Transgenic mice carrying the heterozygous tandem duplication including Fgf8 exhibited proximal shortening of the limbs, resembling the human phenotype. To evaluate whether the phenotype was a result of gene dosage, we generated another transgenic mice line, carrying the duplication on one allele and a concurrent Fgf8 deletion on the other allele, as a control. Surprisingly, the same malformations were observed. Capture Hi-C experiments revealed ectopic interaction with the duplicated region and Fgf8, indicating a position effect. In summary, we show that duplications at the FGF8 locus are associated with femoral hypoplasia and that the phenotype is most likely the result of position effects altering FGF8 expression rather than gene dosage effects.

Published
2021

33. A familial disorder of altered DNA-methylation

Author

Caliebe, Almuth, Richter, Julia, Ammerpohl, Ole, Kanber, Deniz, Beygo, Jasmin, Bens, Susanne, Haake, Andrea, Jüttner, Eva, Korn, Bernhard, Mackay, Deborah J G, Martin-Subero, José I, Nagel, Inga, Sebire, Neil J, Seidmann, Larissa, Vater, Inga, von Kaisenberg, Constantin Sylvius, Temple, I Karen, Horsthemke, Bernhard, Buiting, Karin, and Siebert, Reiner

Published
2014
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35. Partially Levodopa‐Responsive Parkinsonism in a Carrier of a Novel Pathogenic CLTC Variant.

Author

Usnich, Tatiana, Becker, Leonie F., Nagel, Inga, Bäumer, Tobias, and Münchau, Alexander

Subjects
PARKINSONIAN disorders, MOVEMENT disorders, INFORMED consent (Medical law), PARKINSON'S disease, EPILEPSY, FINE motor ability
Abstract

This article discusses a case study of a girl with parkinsonism and developmental delay associated with a variant in the Clathrin heavy chain polypeptide gene (CLTC). The patient showed clinical improvement following Selegiline treatment. Variants in the CLTC gene have been linked to various phenotypes, including developmental delay, hypotonia, epilepsy, and movement disorders. The article highlights the importance of considering pathogenic variants in the CLTC gene as a potential cause of parkinsonism and suggests alternative treatments, such as Amantadine, for managing symptoms. [Extracted from the article]

Published
2024
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36. Molecular characterization of Burkitt lymphoma in the breast or ovary

Author

Elgaafary, Shaymaa, primary, López, Cristina, additional, Nagel, Inga, additional, Vater, Inga, additional, Bens, Susanne, additional, Szczepanowski, Monika, additional, Aukema, Sietse M., additional, Wagener, Rabea, additional, Hopp, Lydia, additional, Binder, Hans, additional, de Leval, Laurence, additional, Klapper, Wolfram, additional, and Siebert, Reiner, additional

Published
2021
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38. The landscape of genomic alterations across childhood cancers

Author

Gröbner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Hübschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jürgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Günther H., Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, Lichter, Peter, Weber, Ursula, Eils, Roland, Korshunov, Andrey, Witt, Olaf, Pfister, Stefan, Reifenberger, Guido, Felsberg, Jörg, von Kalle, Christof, Schmidt, Manfred, Bartholomä, Cynthia, Taylor, Michael, Jones, David, Jäger, Natalie, Korbel, Jan, Stütz, Adrian, Rausch, Tobias, Radlwimmer, Bernhard, Yaspo, Marie-Laure, Lehrach, Hans, Warnatz, Hans-Jörg, Landgraf, Pablo, Brors, Benedikt, Zapatka, Marc, Wagner, Susanne, Haake, Andrea, Richter, Julia, Richter, Gesine, Lawerenz, Chris, Kerssemakers, Jules, Jaeger-Schmidt, Christina, Scholz, Ingrid, Bergmann, Anke K., Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Dreyling, Martin, Eberth, Sonja, Einsele, Hermann, Frickhofen, Norbert, Haas, Siegfried, Hansmann, Martin-Leo, Karsch, Dennis, Kneba, Michael, Lisfeld, Jasmin, Mantovani-Löffler, Luisa, Rohde, Marius, Ott, German, Stadler, Christina, Staib, Peter, Stilgenbauer, Stephan, Trümper, Lorenz, Zenz, Thorsten, Kube, Dieter, Küppers, Ralf, Weniger, Marc, Hummel, Michael, Klapper, Wolfram, Kostezka, Ulrike, Lenze, Dido, Möller, Peter, Rosenwald, Andreas, Szczepanowski, Monika, Ammerpohl, Ole, Aukema, Sietse M., Binder, Vera, Hoell, Jessica I., Leich, Ellen, López, Cristina, Nagel, Inga, Pischimariov, Jordan, Rosenstiel, Philip, Schilhabel, Markus, Schreiber, Stefan, Vater, Inga, Wagener, Rabea, Bernhart, Stephan H., Binder, Hans, Doose, Gero, Hoffmann, Steve, Hopp, Lydia, Kretzmer, Helene, Kreuz, Markus, Langenberger, David, Loeffler, Markus, Rosolowski, Maciej, Schlesner, Matthias, Stadler, Peter F., Sungalee, Stephanie, Kratz, Christian P., van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Frühwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Jones, David T. W., Chavez, Lukas, Pfister, Stefan M., Other departments, CCA - Cancer biology and immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Oncogenomics

Subjects
0301 basic medicine, Adult, Mutation rate, Mutation/genetics, Adolescent, DNA Copy Number Variations, Medizin, Biology, DNA Copy Number Variations/genetics, Germ-Line Mutation/genetics, Germline, Cohort Studies, 03 medical and health sciences, Young Adult, Germline mutation, Neoplasms/classification, Mutation Rate, Neoplasms, medicine, Humans, Genetic Predisposition to Disease, Molecular Targeted Therapy, ddc:610, Mutation frequency, Child, Germ-Line Mutation, Genetics, Chromothripsis, Multidisciplinary, Genome, Human, Genetic Predisposition to Disease/genetics, Cancer, Genomics, medicine.disease, Diploidy, Human genetics, 3. Good health, ddc, 030104 developmental biology, Mutation (genetic algorithm), Mutation, Genome, Human/genetics, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53
Abstract

Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.

Published
2020
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42. BTK acts as a modulator of the response to imatinib in chronic myeloid leukemia.

Author

Schmidlechner, Lena, Nagel, Inga, Vater, Inga, Cascorbi, Ingolf, and Kaehler, Meike

Subjects
*BRUTON tyrosine kinase, *B cell lymphoma, *CHRONIC myeloid leukemia, *PROTEIN-tyrosine kinase inhibitors, *GENE expression, *NILOTINIB
Abstract

The use of tyrosine kinase inhibitors, such as imatinib, against the chronic myeloid leukemia (CML)-causing kinase BCR::ABL1 has become the model for successful targeted therapy. Nevertheless, drug resistance remains a clinical problem. Analysis of genome-wide expression and genetic aberrations of an in vitro imatinib-resistant CML cell line revealed downregulation of Bruton's tyrosine kinase (BTK), predominantly associated with B cell malignancies, and a novel BTK kinase domain variant in imatinib resistance. This raised the question of the role of BTK in imatinib-resistant CML. In the present study, BTK downregulation and the presence of the BTK variant c.1699_1700delinsAG p.(Glu567Arg) were confirmed in imatinib resistance in vitro. Similarly, BTK inhibition or small interfering RNA-mediated BTK knockdown reduced imatinib susceptibility by 84 and 71%, respectively. BTK overexpression was detrimental to CML cells, as proliferation was significantly reduced by 20.5% under imatinib treatment. In addition, BTK rescue in imatinib-resistant cells restored imatinib sensitivity. The presence of the BTK p.(Glu567Arg) variant increased cell numbers (57%) and proliferation (37%) under imatinib exposure. These data demonstrate that BTK is important for the development of imatinib resistance in CML: Its presence increased drug response, while its absence promotes imatinib resistance. Moreover, the BTK p.(Glu567Arg) variant abrogates imatinib sensitivity. These findings demonstrate a context-dependent role for BTK as an oncogene in B cell malignancies, but as a tumor suppressor in other neoplasms. [ABSTRACT FROM AUTHOR]

Published
2024
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44. The mutational landscape of Burkitt-like lymphoma with 11q aberration is distinct from that of Burkitt lymphoma

Author

Wagener, Rabea, Seufert, Julian, Raimondi, Francesco, Bens, Susanne, Kleinheinz, Kortine, Nagel, Inga, Altmüller, Janine, Thiele, Holger, Hübschmann, Daniel, Kohler, Christian W., Nürnberg, Peter, Au-Yeung, Rex, Burkhardt, Birgit, Horn, Heike, Leoncini, Lorenzo, Jaffe, Elaine S., Ott, German, Rymkiewicz, Grzegorz, Schlesner, Matthias, Russell, Robert B., Klapper, Wolfram, and Siebert, Reiner

Published
2019
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46. IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas

Author

Wagener, Rabea, López, Cristina, Kleinheinz, Kortine, Bausinger, Julia, Aukema, Sietse M., Nagel, Inga, Toprak, Umut H., Seufert, Julian, Altmüller, Janine, Thiele, Holger, Schneider, Christof, Kolarova, Julia, Park, Jeongbin, Hübschmann, Daniel, Murga Penas, Eva M., Drexler, Hans G., Attarbaschi, Andishe, Hovland, Randi, Kjeldsen, Eigil, Kneba, Michael, Kontny, Udo, de Leval, Laurence, Nürnberg, Peter, Oschlies, Ilske, Oscier, David, Schlegelberger, Brigitte, Stilgenbauer, Stephan, Wössmann, Wilhelm, Schlesner, Matthias, Burkhardt, Birgit, Klapper, Wolfram, Jaffe, Elaine S., Küppers, Ralf, and Siebert, Reiner

Published
2018
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47. UBTF::ATXN7L3gene fusion defines novel B cell precursor ALL subtype with CDX2 expression and need for intensified treatment

Author

Bastian, Lorenz, Hartmann, Alina M., Beder, Thomas, Hänzelmann, Sonja, Kässens, Jan, Bultmann, Miriam, Hoeppner, Marc P., Franzenburg, Sören, Wittig, Michael, Franke, Andre, Nagel, Inga, Spielmann, Malte, Reimer, Niklas, Busch, Hauke, Schwartz, Stefan, Steffen, Björn, Viardot, Andreas, Döhner, Konstanze, Kondakci, Mustafa, Wulf, Gerald, Wendelin, Knut, Renzelmann, Andrea, Kiani, Alexander, Trautmann, Heiko, Neumann, Martin, Gökbuget, Nicola, Brüggemann, Monika, and Baldus, Claudia D.

Published
2022
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48. IG‐MYC ‐positive leukemia and lymphoma with precursor B‐cell phenotype are genetically and epigenetically distinct from Burkitt lymphomas

Author

Lopez, Cristina, Wagener, Rabea, Kleinheinz, Kortine, Bausinger, Julia, Aukema, Sietse M., Nagel, Inga, Toprak, Umut H., Seufert, Julian, Altmueller, Janine, Thiele, Holger, Schneider, Christof, Kolarova, Julia, Park, Jeongbin, Hübschmann, Daniel, Penas, Eva M. Murga, Drexler, Hans G., Attarbaschi, Andishe, Hovland, Randi, Kjeldsen, Eigil, Kneba, Michael, Kontny, Udo, de Leval, Laurence, Nürnberg, Peter, Oschlies, Ilske, Oscier, David, Schlegelberger, Brigitte, Stilgenbauer, Stephan, Wössmann, Wilhelm, Schlesner, Matthias, Burkhardt, Birgit, Klapper, Wolfram, Jaffe, Elaine S., Küppers, Ralf, and Siebert, Reiner

Subjects
Medizin
Published
2018

49. The landscape of genomic alterations across childhood cancers

Author

Gröbner, Susanne N., Worst, Barbara C., Bender, Sebastian, Lichter, Peter, Jäger, Natalie, Buchhalter, Ivo, Korbel, Jan, Stütz, Adrian, Rausch, Tobias, Radlwimmer, Bernhard, Yaspo, Marie-Laure, Lehrach, Hans, Warnatz, Hans-Jörg, Hutter, Barbara, Landgraf, Pablo, Borkhardt, Arndt, Brors, Benedikt, Zapatka, Marc, Eils, Roland, Eils, Jürgen, Lawerenz, Christian, Siebert, Reiner, Wagner, Susanne, Sturm, Dominik, Haake, Andrea, Richter, Julia, Richter, Gesine, Lawerenz, Chris, Kerssemakers, Jules, Jaeger-Schmidt, Christina, Scholz, Ingrid, Bergmann, Anke K., Pfaff, Elke, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Dreyling, Martin, Eberth, Sonja, Einsele, Hermann, Frickhofen, Norbert, Haas, Siegfried, Hansmann, Martin-Leo, Karsch, Dennis, Hübschmann, Daniel, Kneba, Michael, Lisfeld, Jasmin, Mantovani-Löffler, Luisa, Rohde, Marius, Ott, German, Stadler, Christina, Staib, Peter, Stilgenbauer, Stephan, Trümper, Lorenz, Zenz, Thorsten, Zipprich, Gideon, Kube, Dieter, Küppers, Ralf, Weniger, Marc, Hummel, Michael, Klapper, Wolfram, Kostezka, Ulrike, Lenze, Dido, Möller, Peter, Rosenwald, Andreas, Heinold, Michael, Szczepanowski, Monika, Ammerpohl, Ole, Aukema, Sietse M., Binder, Vera, Hoell, Jessica I., Leich, Ellen, López, Cristina, Nagel, Inga, Pischimariov, Jordan, Rosenstiel, Philip, Schilhabel, Markus, Schreiber, Stefan, Vater, Inga, Wagener, Rabea, Bernhart, Stephan H., Binder, Hans, Doose, Gero, Hoffmann, Steve, Hopp, Lydia, Erkek, Serap, Kleinheinz, Kortine, Kretzmer, Helene, Kreuz, Markus, Langenberger, David, Loeffler, Markus, Rosolowski, Maciej, Schlesner, Matthias, Stadler, Peter F., Sungalee, Stephanie, Weischenfeldt, Joachim, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Hans Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Günther H., Schulte, Johannes, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, ICGC PedBrain-Seq Project, ICGC MMML-Seq Project, Rudneva, Vasilisa A., Kratz, Christian P., Witt, Olaf, van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Frühwald, Michael, von Hoff, Katja, Johann, Pascal D., Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Balasubramanian, Gnana Prakash, Zwijnenburg, Danny A., Raman, Pichai, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Segura-Wang, Maia, Jones, David T. W., Chavez, Lukas, Pfister, Stefan M., Weber, Ursula, Korshunov, Andrey, Brabetz, Sebastian, Pfister, Stefan, Reifenberger, Guido, Felsberg, Jörg, von Kalle, Christof, Schmidt, Manfred, Bartholomä, Cynthia, Taylor, Michael, and Jones, David

Published
2018
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