| Title: |
HGG-16. Pediatric-type diffuse high-grade glioma of methylation-based RTK2A and RTK2B subclasses present distinct radiological and histomolecular features [Abstract] |
| Authors: |
Tauziède-Espariat, Arnault; Friker, Lea L.; Nussbaumer, Gunther; Alice, Métais; Antonelli, Manila; Benesch, Martin; Bison, Brigitte; Dangouloff-Ros, Volodia; Garrè, Maria Luisa; Giangaspero, Felice; Grabovska, Yura; Grill, Jacques; Jones, David T. W.; Jones, Chris; Karremann, Michael; Kramm, Christof M.; Mackay, Alan; Morales La Madrid, Andrés; Perwein, Thomas; Pietsch, Torsten; Sumerauer, David; van Vuurden, Dannis; von Bueren, André O.; Warmuth-Metz, Monika; Wesseling, Pieter; Zamecnik, Josef; Castel, David; Gielen, Gerrit H.; Varlet, Pascale |
| Publication Year: |
2024 |
| Collection: |
Augsburg University Publication Server (OPUS) |
| Subject Terms: |
ddc:610 |
| Description: |
BACKGROUND Diffuse pediatric-type high-grade gliomas (pedHGG), H3-wildtype and IDH-wildtype, encompass three main methylome-based subclasses: pedHGG-MYCN, -RTK1A/B/C, and -RTK2A/B. Since their first description in 2017, tumors of pedHGG-RTK2A/B have not been further characterized and their clinical significance is unknown. METHODS A not yet published cases series on pedHGG with a gliomatosis cerebri (GC) growth pattern showed an increased incidence of pedHGG-RTK2A/B (n=18/40). We assembled a cohort of 14 additional methylation-based pedHGG-RTK2A/B tumors and pooled them with the GC tumors providing centrally reviewed radiological, histological, and molecular characterization. RESULTS Our cohort of 32 pedHGG-RTK2A/B tumors consisted of 25 RTK2A (78%) and seven RTK2B (22%) cases. The median age was 11.6 years (4-17) with an overall survival of 15.9 months (interquartile range 12.1-25.8). Of the additional unselected cases with available imaging (10 of 14), seven showed a GC phenotype at diagnosis or follow-up. In addition, pedHGG-RTK2B tumors exhibited bithalamic involvement (6/7, 86%). Histopathology confirmed a diffuse glial neoplasm in all cases with prominent angiocentric features in both subclasses. Most tumors (24/29, 83%) diffusely expressed EGFR, notably with a focal perivascular enhancement. Cells of pedHGG-RTK2A lacked Olig2 expression, whereas 43% (3/7) of pedHGG-RTK2B expressed Olig2. Loss of ATRX expression occurred in four pedHGG-RTK2B samples (57%). In sequencing analyses (RTK2A: n=18, RTK2B: n=5), EGFR alterations (n=15/23, 65%; predominantly point mutations) were commonly found in both subclasses. Mutations in BCOR (n=14/18, 78%), SETD2 (n=7/18, 39%), and TERT promoter (n=6/18, 33%) occurred exclusively in pedHGG-RTK2A tumors, while pedHGG-RTK2B tumors were enriched for TP53 mutations (4/5, 80%). CONCLUSIONS In conclusion, genotype-phenotype correlations in a multicenter series of pedHGG-RTK2A/B tumors revealed a highly diffuse-infiltrating tumor frequently exhibiting a GC phenotype. The two ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://doi.org/10.1093/neuonc/noae064.300 |
| DOI: |
10.1093/neuonc/noae064.300 |
| Availability: |
https://opus.bibliothek.uni-augsburg.de/opus4/frontdoor/index/index/docId/115398; https://nbn-resolving.org/urn:nbn:de:bvb:384-opus4-1153988; https://doi.org/10.1093/neuonc/noae064.300; https://opus.bibliothek.uni-augsburg.de/opus4/files/115398/noae064.300.pdf |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/deed.de ; CC-BY-NC 4.0: Creative Commons: Namensnennung - Nicht kommerziell (mit Print on Demand) ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.DB459843 |
| Database: |
BASE |