| Title: |
Gliomatosis cerebri in children : A poor prognostic phenotype of diffuse gliomas with a distinct molecular 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; Pentikainen, 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; Warmuth-Metz, Monika; Wesseling, Pieter; Wiese, Maria; Wolff, Johannes E A; Zamecnik, Josef; Morales La Madrid, Andrés; Bison, Brigitte; Gielen, Gerrit H; Jones, David T W; Jones, Chris; Kramm, Christof M |
| Source: |
ISSN: 1522-8517 ; Neuro-oncology, vol. 26, no. 9 (2024) p. 1723-1737. |
| Publication Year: |
2024 |
| Collection: |
Université de Genève: Archive ouverte UNIGE |
| Subject Terms: |
info:eu-repo/classification/ddc/618; H3-wild-type and IDH-wild-type; Chromosome 6; Gliomatosis cerebri; PedHGG_RTK2; Pediatric-type glioma; Pediatric-type high-grade glioma; Humans; Child; Male; Neoplasms; Neuroepithelial / pathology; Neuroepithelial / genetics; Female; Adolescent; Retrospective Studies; Prognosis; Preschool; Brain Neoplasms / genetics; Brain Neoplasms / pathology; Glioma / genetics; Glioma / pathology; Phenotype; Survival Rate; DNA Methylation; Infant; Biomarkers; Tumor / genetics; Mutation; Follow-Up Studies |
| 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). |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38717379; unige:181993 |
| Availability: |
https://archive-ouverte.unige.ch/unige:181993 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.5F6D841 |
| Database: |
BASE |