% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{TauzideEspariat:294583, author = {A. Tauziède-Espariat and L. L. Friker and G. Nussbaumer and B. Bison and V. Dangouloff-Ros and A. Métais and D. Sumerauer and J. Zamecnik and M. Benesch and T. Perwein and D. van Vuurden and P. Wesseling and A. M. La Madrid and M. L. Garrè and M. Antonelli and F. Giangaspero and T. Pietsch and D. Sturm$^*$ and D. T. W. Jones$^*$ and S. M. Pfister$^*$ and Y. Grabovska and A. Mackay and C. Jones and J. Grill and Y. Ajlil and A. O. von Bueren and M. Karremann and M. Hoffmann and C. M. Kramm and R. Kwiecien and D. Castel and G. H. Gielen and P. Varlet}, title = {{D}iffuse pediatric high-grade glioma of methylation-based {RTK}2{A} and {RTK}2{B} subclasses present distinct radiological and histomolecular features including {G}liomatosis cerebri phenotype.}, journal = {Acta Neuropathologica Communications}, volume = {12}, number = {1}, issn = {2051-5960}, address = {London}, publisher = {Biomed Central}, reportid = {DKFZ-2024-02358}, pages = {176}, year = {2024}, abstract = {Diffuse pediatric-type high-grade gliomas (pedHGG), H3- and IDH-wildtype, encompass three main DNA-methylation-based subtypes: pedHGG-MYCN, pedHGG-RTK1A/B/C, and pedHGG-RTK2A/B. Since their first description in 2017 tumors of pedHGG-RTK2A/B have not been comprehensively characterized and clinical correlates remain elusive. In a recent series of pedHGG with a Gliomatosis cerebri (GC) growth pattern, an increased incidence of pedHGG-RTK2A/B (n = 18) was observed. We added 14 epigenetically defined pedHGG-RTK2A/B tumors to this GC series and provided centrally reviewed radiological, histological, and molecular characterization. The final cohort of 32 pedHGG-RTK2A/B tumors consisted of 25 pedHGG-RTK2A $(78\%)$ and seven pedHGG-RTK2B $(22\%)$ cases. The median age was 11.6 years (range, 4-17) with a median overall survival of 16.0 months (range 10.9-28.2). Seven of 11 of the newly added cases with imaging available showed a GC phenotype at diagnosis or follow-up. PedHGG-RTK2B tumors exhibited frequent bithalamic involvement (6/7, $86\%).$ Central neuropathology review confirmed a diffuse glial neoplasm in all tumors with prominent angiocentric features in both subclasses. Most tumors (24/27 with available data, $89\%)$ diffusely expressed EGFR with focal angiocentric enhancement. PedHGG-RTK2A tumors lacked OLIG2 expression, whereas $43\%$ (3/7) of pedHGG-RTK2B expressed this glial transcription factor. ATRX loss occurred in 3/6 pedHGG-RTK2B samples with available data $(50\%).$ DNA sequencing (pedHGG-RTK2A: n = 18, pedHGG-RTK2B: n = 5) found EGFR alterations (15/23, $65\%;$ predominantly point mutations) in both subclasses. Mutations in BCOR (14/18, $78\%),$ SETD2 (7/18, $39\%),$ and the hTERT promoter (7/19, $37\%)$ occurred exclusively in pedHGG-RTK2A tumors, while pedHGG-RTK2B tumors were enriched for TP53 alterations (4/5, $80\%).$ In conclusion, pedHGG-RTK2A/B tumors are characterized by highly diffuse-infiltrating growth patterns and specific radiological and histo-molecular features. By comprehensively characterizing methylation-based tumors, the chance to develop specific and effective therapy concepts for these detrimental tumors increases.}, keywords = {Humans / Child / Male / Female / Brain Neoplasms: genetics / Brain Neoplasms: pathology / Brain Neoplasms: diagnostic imaging / Adolescent / Child, Preschool / Neoplasms, Neuroepithelial: genetics / Neoplasms, Neuroepithelial: pathology / Neoplasms, Neuroepithelial: diagnostic imaging / DNA Methylation / Glioma: genetics / Glioma: pathology / Glioma: diagnostic imaging / Phenotype / Gliomatosis cerebri (Other) / Methylation (Other) / Pediatric high-grade glioma (Other) / RTK2A (Other) / RTK2B (Other) / Receptor tyrosine kinase (Other) / pedHGG (Other)}, cin = {B360 / B062 / HD01}, ddc = {610}, cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331}, pnm = {312 - Funktionelle und strukturelle Genomforschung (POF4-312)}, pid = {G:(DE-HGF)POF4-312}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:39558399}, pmc = {pmc:PMC11575044}, doi = {10.1186/s40478-024-01881-1}, url = {https://inrepo02.dkfz.de/record/294583}, }