Scientific publications
Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile. Scientific Publication
Gunther Nussbaumer 1 , Martin Benesch 1 , Yura Grabovska 2 , Alan Mackay 2 , David Castel 3 4 , Jacques Grill 3 4 , Marta M Alonso 5 6 7 , Manila Antonelli 8 , Simon Bailey 9 , Joshua N Baugh 10 , Veronica Biassoni 11 , Mirjam Blattner Johnson 12 13 , Alberto Broniscer 14 , Andrea Carai 15 , Giovanna Stefania Colafati 16 , Niclas Colditz 17 , Selim Corbacioglu 18 , Shauna Crampsie 2 , Natacha Entz-Werle 19 20 , Matthias Eyrich 21 , Lea L Friker 22 , Michael C Frühwald 23 , Maria Luisa Garrè 24 , Nicolas U Gerber 25 , Felice Giangaspero 8 , Maria J Gil-da-Costa 26 , Norbert Graf 27 , Darren Hargrave 28 , Peter Hauser 29 , Ulrich Herrlinger 30 , Marion Hoffmann 17 , Esther Hulleman 10 , Elisa Izquierdo 2 , Sandra Jacobs 31 , Michael Karremann 32 , Antonis Kattamis 33 , Rejin Kebudi 34 , Rolf-Dieter Kortmann 35 , Robert Kwiecien 36 , Maura Massimino 11 , Angela Mastronuzzi 37 , Evelina Miele 37 , Giovanni Morana 38 , Claudia M Noack 39 , Virve Pentikainen 40 , Thomas Perwein 1 , Stefan M Pfister 12 41 42 43 , Torsten Pietsch 22 , Kleoniki Roka 33 , Sabrina Rossi 44 , Stefan Rutkowski 45 , Elisabetta Schiavello 11 , Clemens Seidel 35 , Jaroslav Štěrba 46 , Dominik Sturm 12 13 42 , David Sumerauer 47 , Anna Tacke 17 , Sara Temelso 2 , Chiara Valentini 48 , Dannis van Vuurden 10 , Pascale Varlet 49 , Sophie E M Veldhuijzen van Zanten 10 50 , Maria Vinci 37 , André O von Bueren 51 , Monika Warmuth-Metz 52 , Pieter Wesseling 10 53 , Maria Wiese 15 , Johannes E A Wolff 54 , Josef Zamecnik 55 , Andrés Morales La Madrid 56 , Brigitte Bison 57 58 , Gerrit H Gielen 22 , David T W Jones 12 13 , Chris Jones 2 , Christof M Kramm 17
Background: The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet.
Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization.
Results: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-years survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n=49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wildtype (n=31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n=19), pedHGG_A/B (n=6), and pedHGG_MYCN (n=5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wildtype subgroup, recurrent alterations in EGFR (n=10) and BCOR (n=9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wildtype subgroup TP53 alterations had a significant negative effect on OS.
Conclusion: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).
CITATION Neuro Oncol. 2024 May 8:noae080. doi: 10.1093/neuonc/noae080
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