Nussbaumer, Gunther;
Benesch, Martin;
Grabovska, Yura;
Mackay, Alan;
Castel, David;
Grill, Jacques;
Alonso, Marta M;
... Kramm, Christof M; + view all
(2024)
Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.
Neuro-Oncology
, 26
(9)
pp. 1723-1737.
10.1093/neuonc/noae080.
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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).
| Type: | Article |
|---|---|
| Title: | Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/neuonc/noae080 |
| Publisher version: | https://doi.org/10.1093/neuonc/noae080 |
| Language: | English |
| Additional information: | © The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | chromosome 6, gliomatosis cerebri, H3-wild-type and IDH-wild-type, pedHGG_RTK2, pediatric-type glioma, pediatric-type high-grade glioma |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10214537 |
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