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Atypical teratoid/rhabdoid tumors are comprised of three epigenetic subgroups with distinct enhancer landscapes

Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigeneti...

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Main Authors: Johann, Pascal-David (Author) , Sturm, Dominik (Author) , Korshunov, Andrey (Author) , Gröschel, Stefan (Author) , Geörg, Christina (Author) , Capper, David (Author) , Deimling, Andreas von (Author) , Milde, Till (Author) , Witt, Olaf (Author) , Kulozik, Andreas (Author) , Pfister, Stefan (Author)
Format: Article (Journal)
Language:English
Published: February 25, 2016
In: Cancer cell
Year: 2016, Volume: 29, Issue: 3, Pages: 379-393
ISSN:1878-3686
DOI:10.1016/j.ccell.2016.02.001
Online Access:Verlag, Volltext: https://doi.org/10.1016/j.ccell.2016.02.001
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610816300356
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Author Notes:Pascal D. Johann, Serap Erkek, Marc Zapatka, Kornelius Kerl, Ivo Buchhalter, Volker Hovestadt, David T. W. Jones, Dominik Sturm, Carl Hermann, Maia Segura Wang, Andrey Korshunov, Marina Rhyzova, Susanne Gröbner, Sebastian Brabetz, Lukas Chavez, Susanne Bens, Stefan Gröschel, Fabian Kratochwil, Andrea Wittmann, Laura Sieber, Christina Geörg, Stefan Wolf, Katja Beck, Florian Oyen, David Capper, Peter van Sluis, Richard Volckmann, Jan Koster, Rogier Versteeg, Andreas von Deimling, Till Milde, Olaf Witt, Andreas E. Kulozik, Martin Ebinger, Tarek Shalaby, Michael Grotzer, David Sumerauer, Josef Zamecnik, Jaume Mora, Nada Jabado, Michael D. Taylor, Annie Huang, Eleonora Aronica, Anna Bertoni, Bernhard Radlwimmer, Torsten Pietsch, Ulrich Schüller, Reinhard Schneppenheim, Paul A. Northcott, Jan O. Korbel, Reiner Siebert, Michael C. Frühwald, Peter Lichter, Roland Eils, Amar Gajjar, Martin Hasselblatt, Stefan M. Pfister, and Marcel Kool
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Summary:Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Item Description:Gesehen am 21.02.2020
Physical Description:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2016.02.001

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