Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma
Sturm, Dominik; Witt, Hendrik; Hovestadt, Volker; Khuong-Quang, Dong-Anh; Jones, David TW; 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; Hauser, Péter; Garami, Miklós; Klekner, Álmos; Bognár, László; Sorana, Morrissy; Florence, Cavalli; Michael, D Taylor; Peter, van Sluis; Jan, Koste; 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;
Folyóiratcikk
CANCER CELL
vol.:22,
issue.:4,
p.:425-437.
ISSN: 1535-6108
WoS ID:
000310113900005
PubMed ID:
23079654
Megjelenés éve:
2012
Kivonat:
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.
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