Nussbaumer, Gunther and Benesch, Martin and Grabovska, Yura and Mackay, Alan and Castel, David and Grill, Jacques and Alonso, Marta M. and Antonelli, Manila and Bailey, Simon and Baugh, Joshua N. and Biassoni, Veronica and Blattner-Johnson, Mirjam and Broniscer, Alberto and Carai, Andrea and Colafati, Giovanna Stefania and Colditz, Niclas and Corbacioglu, Selim and Crampsie, Shauna and Entz-Werle, Natacha and Eyrich, Matthias and Friker, Lea L. and Fruehwald, Michael C. and Garre, Maria Luisa and Gerber, Nicolas U. and Giangaspero, Felice and Gil-da-Costa, Maria J. and Graf, Norbert and Hargrave, Darren and Hauser, Peter and Herrlinger, Ulrich and Hoffmann, Marion and Hulleman, Esther and Izquierdo, Elisa and Jacobs, Sandra and Karremann, Michael and Kattamis, Antonis and Kebudi, Rejin and Kortmann, Rolf-Dieter and Kwiecien, Robert and Massimino, Maura and Mastronuzzi, Angela and Miele, Evelina and Morana, Giovanni and Noack, Claudia M. and Pentikainen, Virve and Perwein, Thomas and Pfister, Stefan M. and Pietsch, Torsten and Roka, Kleoniki and Rossi, Sabrina and Rutkowski, Stefan and Schiavello, Elisabetta and Seidel, Clemens and Sterba, Jaroslav and Sturm, Dominik and Sumerauer, David and Tacke, Anna and Temelso, Sara and Valentini, Chiara and van Vuurden, Dannis and Varlet, Pascale and van Zanten, Sophie E. M. Veldhuijzen and Vinci, Maria and von Bueren, Andre O. and Warmuth-Metz, Monika and Wesseling, Pieter and Wiese, Maria and Wolff, Johannes E. A. and Zamecnik, Josef and Morales La Madrid, Andres and Bison, Brigitte and Gielen, Gerrit H. and Jones, David T. W. and Jones, Chris and Kramm, Christof M. (2024) Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile. NEURO-ONCOLOGY, 26 (9). pp. 1723-1737. ISSN 1522-8517, 1523-5866
Full text not available from this repository. (Request a copy)Abstract
Background. The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established. 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-year 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-wild-type (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-wild-type 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-wild-type subgroup TP53 alterations had a significant negative effect on OS. Conclusions. 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). Key Points The presence of gliomatosis cerebri (GC) phenotype may be considered as an independent dismal prognostic factor in hemispheric pediatric-type diffuse gliomas. The methylome-based subtypes pediatric-type diffuse high-grade glioma (pedHGG)_RTK2A/B and (provisional) pedHGG_A/B were significantly associated with GC. EGFR and BCOR alterations and rearrangements of chromosome 6 were the most common genetic features in pediatric GC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PEDIATRIC HIGH-GRADE; MUTATIONS; ONCOLOGY; LOMUSTINE; GENES; chromosome 6; gliomatosis cerebri; H3-wild-type and IDH-wild-type; pedHGG_RTK2; pediatric-type glioma; pediatric-type high-grade glioma |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jul 2025 09:23 |
| Last Modified: | 23 Jul 2025 09:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65755 |
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