作者
Dominik Sturm, Hendrik Witt, Volker Hovestadt, Dong-Anh Khuong-Quang, David TW Jones, Carolin Konermann, Elke Pfaff, Martje Tönjes, Martin Sill, Sebastian Bender, Marcel Kool, Marc Zapatka, Natalia Becker, Manuela Zucknick, Thomas Hielscher, Xiao-Yang Liu, Adam M Fontebasso, Marina Ryzhova, Steffen Albrecht, Karine Jacob, Marietta Wolter, Martin Ebinger, Martin U Schuhmann, Timothy van Meter, Michael C Frühwald, Holger Hauch, Arnulf Pekrun, Bernhard Radlwimmer, Tim Niehues, Gregor Von Komorowski, Matthias Dürken, Andreas E Kulozik, Jenny Madden, Andrew Donson, Nicholas K Foreman, Rachid Drissi, Maryam Fouladi, Wolfram Scheurlen, Andreas von Deimling, Camelia Monoranu, Wolfgang Roggendorf, Christel Herold-Mende, Andreas Unterberg, Christof M Kramm, Jörg Felsberg, Christian Hartmann, Benedikt Wiestler, Wolfgang Wick, Till Milde, Olaf Witt, Anders M Lindroth, Jeremy Schwartzentruber, Damien Faury, Adam Fleming, Magdalena Zakrzewska, Pawel P Liberski, Krzysztof Zakrzewski, Peter Hauser, Miklos Garami, Almos Klekner, Laszlo Bognar, Sorana Morrissy, Florence Cavalli, Michael D Taylor, Peter van Sluis, Jan Koster, Rogier Versteeg, Richard Volckmann, Tom Mikkelsen, Kenneth Aldape, Guido Reifenberger, V Peter Collins, Jacek Majewski, Andrey Korshunov, Peter Lichter, Christoph Plass, Nada Jabado, Stefan M Pfister
发表日期
2012/10/16
期刊
Cancer cell
卷号
22
期号
4
页码范围
425-437
出版商
Elsevier
简介
Glioblastoma (GBM) is a brain tumor that carries a dismal prognosis and displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical amino acids (K27 and G34) of histone H3.3 in one-third of pediatric GBM. Here, we show that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup. Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM and/or established transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of transcription factors OLIG1, OLIG2, and FOXG1, possibly reflecting different cellular origins.
学术搜索中的文章
D Sturm, H Witt, V Hovestadt, DA Khuong-Quang… - Cancer cell, 2012