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Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes

2016; Cell Press; Volume: 29; Issue: 3 Linguagem: Inglês

10.1016/j.ccell.2016.02.001

1878-3686

Pascal D. Johann, Serap Erkek, Marc Zapatka, Kornelius Kerl, Ivo Buchhalter, Volker Hovestadt, David Jones, Dominik Sturm, Carl Hermann, Maia Segura‐Wang, Andrey Korshunov, Marina Rhyzova, Susanne Gröbner, Sebastian Brabetz, Lukas Chávez, 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 Köster, Rogier Versteeg, Andreas von Deimling, Till Milde, Olaf Witt, Andreas E. Kulozik, Martin Ebinger, Tarek Shalaby, Michael Grotzer, David Sumerauer, Josef Zámečnı́k, 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, Marcel Kool,

Protein Degradation and Inhibitors

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.