| Title: |
Gliomatosis cerebri in children : A poor prognostic phenotype of diffuse gliomas with a distinct molecul profile |
| Authors: |
Nussbaumer, Gunther; Benesch, Martin; Grabovska, Yura; Mackay, Alan; Castel, David; Grill, Jacques; Alonso, Marta M.; Antonelli, Manila; Bailey, Simon; Baugh, Joshua N.; Biassoni, Veronica; Blattner-Johnson, Mirjam; Broniscer, Alberto; Carai, Andrea; Colafati, Giovanna Stefania; Colditz, Niclas; Corbacioglu, Selim; Crampsie, Shauna; Entz-Werle, Natacha; Eyrich, Matthias; Friker, Lea L.; Frühwald, Michael C.; Garrè, Maria Luisa; Gerber, Nicolas U.; Giangaspero, Felice; Gil-Da-Costa, Maria J.; Graf, Norbert; Hargrave, Darren; Hauser, Peter; Herrlinger, Ulrich; Hoffmann, Marion; Hulleman, Esther; Izquierdo, Elisa; Jacobs, Sandra; Karremann, Michael; Kattamis, Antonis; Kebudi, Rejin; Kortmann, Rolf Dieter; Kwiecien, Robert; Massimino, Maura; Mastronuzzi, Angela; Miele, Evelina; Morana, Giovanni; Noack, Claudia M.; Pentikäinen, Virve; Perwein, Thomas; Pfister, Stefan M.; Pietsch, Torsten; Roka, Kleoniki; Rossi, Sabrina; Rutkowski, Stefan; Schiavello, Elisabetta; Seidel, Clemens; Štěrba, Jaroslav; Sturm, Dominik; Sumerauer, David; Tacke, Anna; Temelso, Sara; Valentini, Chiara; van Vuurden, Dannis; Varlet, Pascale; Veldhuijzen van Zanten, Sophie E.M.; Vinci, Maria; von Bueren, André O.; Warmuth-Metz, Monika; Wesseling, Pieter; Wiese, Maria; Wolff, Johannes E.A.; Zamecnik, Josef; La Madrid, Andrés Morales; Bison, Brigitte; Gielen, Gerrit H.; Jones, David T.W.; Jones, Chris; Kramm, Christof M. |
| Contributors: |
HUS Children and Adolescents; Children's Hospital |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2025 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
chromosome 6; gliomatosis cerebri; H3-wild-type and; IDH-wild-type; pedHGG_RTK2; pediatric-type glioma; pediatric-type high-grade glioma; Gynaecology and paediatrics |
| Description: |
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). ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
38717379 |
| Relation: |
This study including the Neuroradiological Reference Center in Augsburg (B.B.), formerly in M\u00FCnster (M.W.-M.), the Neuropathological Reference Center in Bonn (T.Pi.), the Reference Center for Radiation Oncology in Dresden (C.V.), and the HIT-HGG/ GBM Studies (M.H., C.M.K., and G.N., T.Pe., M.B.) were supported by the German- and Styrian Childhood Cancer Foundation (\u201CDeutsche Kinderkrebsstiftung,\u201D \u201CSteirische Kinderkrebshilfe\u201D), respectively. D.C. and J.G. acknowledge funding from \u201CEtoile de Martin\u201D and \u201CLes Boucles du C\u0153ur de la Fondation Carrefour\u201D for the project RARE, and support from the Necker Imagine Tumor and DNA biobank (BB-033-00065). C.J. acknowledges funding from the \u201CRudy A Menon Foundation\u201D, \u201CCRIS Cancer Foundation\u201D, the \u201COllie Young Foundation\u201D, \u201CCancer Research UK\u201D (C13468/ A23536, DRCRPG-Nov21\\100002) and the Joshua Bembo Project, as well as NHS funding to the ICR/RMH Biomedical Research Centre, and is recipient of joint grant support from Izas la princesa guisante, L\u2019union des rayons de soleils and the AYJ Fund. D.H. is supported by funding from the NIHR Great Ormond Street Hospital Biomedical Research Centre. The Pediatric Cancer Center Barcelona (A.M.L.M) acknowledges funding from the \u201CIzas, la Princesa Guisante Foundation.\u201D D.S. acknowledges funding from PRIMUS/19/MED/06, Charles University Grant Agency, Czech Republic. The Bambino Ges\u00F9 Children\u2019s Hospital (A.C., G.St.C, A.M., E.M., S.Ro., M.V.) acknowledges funding from \u201CFondazione Heal,\u201D \u201CIl Coraggio dei Bambini,\u201D \u201CMartina e La Sua Luna\u201D and \u201CIl laboratorio di Chiara.\u201D M.M. acknowledges funding from the Italian Ministry of Health and by Regione Lombardia (project ID NET-2019-12371188). M.L.G. acknowledges support by the Italian Ministry of Health and by Regione Liguria (Ricerca Finalizzata di Rete NET-2019-12371188, GLI-HOPE). We thank Mike Hubank (Royal Marsden Hospital) and Theresa Hammerl (Graz University of Technology) for technical assistance. We remember and thank Prof. Felice Giangaspero for his life-long dedication to childhood brain tumors. This study including the Neuroradiological Reference Center in Augsburg (B.B.), formerly in M\u00FCnster (M.W.-M.), the Neuropathological Reference Center in Bonn (T.Pi.), the Reference Center for Radiation Oncology in Dresden (C.V.), and the HIT-HGG/GBM Studies (M.H., C.M.K., and G.N., T.Pe., M.B.) were supported by the German- and Styrian Childhood Cancer Foundation (\u201CDeutsche Kinderkrebsstiftung,\u201D \u201CSteirische Kinderkrebshilfe\u201D), respectively. D.C. and J.G. acknowledge funding from \u201CEtoile de Martin\u201D and \u201CLes Boucles du C\u0153ur de la Fondation Carrefour\u201D for the project RARE, and support from the Necker Imagine Tumor and DNA biobank (BB-033-00065). C.J. acknowledges funding from the \u201CRudy A Menon Foundation\u201D, \u201CCRIS Cancer Foundation\u201D, the \u201COllie Young Foundation\u201D, \u201CCancer Research UK\u201D (C13468/A23536, DRCRPG-Nov21\\100002) and the Joshua Bembo Project, as well as NHS funding to the ICR/RMH Biomedical Research Centre, and is recipient of joint grant support from Izas la princesa guisante, L\u2019union des rayons de soleils and the AYJ Fund. D.H. is supported by funding from the NIHR Great Ormond Street Hospital Biomedical Research Centre. The Pediatric Cancer Center Barcelona (A.M.L.M) acknowledges funding from the \u201CIzas, la Princesa Guisante Foundation.\u201D D.S. acknowledges funding from PRIMUS/19/MED/06, Charles University Grant Agency, Czech Republic. The Bambino Ges\u00F9 Children\u2019s Hospital (A.C., G.St.C, A.M., E.M., S.Ro., M.V.) acknowledges funding from \u201CFondazione Heal,\u201D \u201CIl Coraggio dei Bambini,\u201D \u201CMartina e La Sua Luna\u201D and \u201CIl laboratorio di Chiara.\u201D M.M. acknowledges funding from the Italian Ministry of Health and by Regione Lombardia (project ID NET-2019-12371188). M.L.G. acknowledges support by the Italian Ministry of Health and by Regione Liguria (Ricerca Finalizzata di Rete NET-2019-12371188, GLI-HOPE). Acknowledgments; https://hdl.handle.net/10138/592234; 85199676724; 001458375800001 |
| Availability: |
https://hdl.handle.net/10138/592234 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.B2F8D550 |
| Database: |
BASE |