The whole-genome landscape of medulloblastoma subtypes
| Autor: | Daniel Hübschmann, Olaf Witt, Eric Chuah, Michael Heinold, Andrey Korshunov, Zuguang Gu, Vyacheslav Amstislavskiy, Aaron H. Phillips, Matthias Bieg, David Finkelstein, Thomas Risch, Nikos Sidiropoulos, Peter Lichter, Tina Wong, Yanling Liu, Roland Eils, Barbara Hutter, Marc Zapatka, Sebastian M. Waszak, Charles D. Imbusch, Roger E. McLendon, Marie-Laure Yaspo, Susanne Gröbner, Volker Hovestadt, Ernest Fraenkel, Martin Ebinger, Florence M.G. Cavalli, Steven E. Schumacher, Hans-Jörg Warnatz, Amar Gajjar, Tobias Ehrenberger, Michael D. Taylor, Ivo Buchhalter, Kane Tse, Betty Luu, Ursula D. Weber, Christel Herold-Mende, Benedikt Brors, Vasilisa A. Rudneva, Barbara C. Worst, Scott L. Pomeroy, Jinghui Zhang, Martin U. Schuhmann, Marina Ryzhova, Stephan Wolf, Andrew J. Mungall, Xin Zhou, Matthias Schlesner, A. Sorana Morrissy, Nagarajan Paramasivam, Maia Segura-Wang, Jan Koster, Stefan M. Pfister, Joachim Weischenfeldt, Marcel Kool, Yoon Jae Cho, Kortine Kleinheinz, Natalie Jäger, Richard A. Moore, Toshihiro Kumabe, Rameen Beroukhim, David Capper, Vijay Ramaswamy, Gang Wu, Linda M. Liau, Francisco German Rodriguez Gonzalez, Xiaochong Wu, Karen Mungall, Jan O. Korbel, Christina Jäger-Schmidt, Alke Jugold, Serap Erkek, Andreas von Deimling, Richard W. Kriwacki, Steven J.M. Jones, Thomas Zichner, Paul A. Northcott, David T.W. Jones, Lukas Chavez, Till Milde, Jaume Mora, Marco A. Marra, Yussanne Ma, Naveed Ishaque, Nina Thiessen, Nada Jabado, Giles W. Robinson |
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| Přispěvatelé: | Other departments, CCA - Cancer biology and immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Oncogenomics, Massachusetts Institute of Technology. Department of Biological Engineering, Ehrenberger, Tobias, Fraenkel, Ernest |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Carcinogenesis DNA Mutational Analysis Datasets as Topic Muscle Proteins medicine.disease_cause Bioinformatics Genome Cohort Studies 2.1 Biological and endogenous factors Molecular Targeted Therapy Aetiology Cancer Pediatric Multidisciplinary Genomics 5.1 Pharmaceuticals DNA methylation Development of treatments and therapeutic interventions Human Biotechnology Pediatric Cancer General Science & Technology Biology Article 03 medical and health sciences Rare Diseases Genetic medicine Genetics Humans ddc:610 Gene Medulloblastoma Whole Genome Sequencing Genome Human Human Genome Neurosciences Epistasis Genetic Oncogenes DNA Methylation medicine.disease Human genetics Brain Disorders Brain Cancer Wnt Proteins 030104 developmental biology Good Health and Well Being Mutation Epistasis Human genome Carrier Proteins Transcription Factors |
| Zdroj: | Nature r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname Nature, vol 547, iss 7663 Northcott, P A, Buchhalter, I, Morrissy, A S, Hovestadt, V, Weischenfeldt, J, Ehrenberger, T, Gröbner, S, Segura-Wang, M, Zichner, T, Rudneva, V A, Warnatz, H J, Sidiropoulos, N, Phillips, A H, Schumacher, S, Kleinheinz, K, Waszak, S M, Erkek, S, Jones, D T W, Worst, B C, Kool, M, Zapatka, M, Jäger, N, Chavez, L, Hutter, B, Bieg, M, Paramasivam, N, Heinold, M, Gu, Z, Ishaque, N, Jäger-Schmidt, C, Imbusch, C D, Jugold, A, Hübschmann, D, Risch, T, Amstislavskiy, V, Gonzalez, F G R, Weber, U D, Wolf, S, Robinson, G W, Zhou, X, Wu, G, Finkelstein, D, Liu, Y, Cavalli, F M G, Luu, B, Ramaswamy, V, Wu, X, Koster, J, Ryzhova, M, Cho, Y J, Pomeroy, S L, Herold-Mende, C, Schuhmann, M, Ebinger, M, Liau, L M, Mora, J, McLendon, R E, Jabado, N, Kumabe, T, Chuah, E, Ma, Y, Moore, R A, Mungall, A J, Mungall, K L, Thiessen, N, Tse, K, Wong, T, Jones, S J M, Witt, O, Milde, T, Von Deimling, A, Capper, D, Korshunov, A, Yaspo, M L, Kriwacki, R, Gajjar, A, Zhang, J, Beroukhim, R, Fraenkel, E, Korbel, J O, Brors, B, Schlesner, M, Eils, R, Marra, M A, Pfister, S M, Taylor, M D & Lichter, P 2017, ' The whole-genome landscape of medulloblastoma subtypes ', Nature, vol. 547, no. 7663, pp. 311-317 . https://doi.org/10.1038/nature22973 Nature, 547(7663), 311-317. Nature Publishing Group r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu |
| ISSN: | 0028-0836 |
| Popis: | Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma. |
| Databáze: | OpenAIRE |
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