Journal Article

DKFZ-2024-01377

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Characteristics of H3K27M-mutant diffuse gliomas with a non-midline location.

Guidara, S. ; Seyve, A. ; Poncet, D. ; Leonce, C. ; Bringuier, P.-P. ; McLeer, A. ; Sturm, D.DKFZ* ; Cartalat, S. ; Picart, T. ; Ferrari, A. ; Hench, J. ; Frank, S. ; Meyronet, D. ; Ducray, F. ; Barritault, M.

2024
Springer Science + Business Media B.V Dordrecht [u.a.]

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Please use a persistent id in citations: doi:10.1007/s11060-024-04733-z

Abstract: Diffuse midline gliomas (DMG) with H3K27 alterations (H3K27M-DMG) are a highly aggressive form of brain cancer. In rare cases, H3K27 mutations have been observed in diffuse non-midline gliomas (DNMG). It is currently unclear how these tumors should be classified. Herein, we analyze the characteristics of DNMG with H3K27M mutations.We reviewed the clinical, radiological and histological characteristics of all patients with an H3K27M mutated diffuse glioma diagnosed in our institution, between 2016 and 2023, to identify cases with a non-midline location. We then performed a molecular characterization (DNA methylation profiling, whole genome and transcriptome sequencing or targeted sequencing) of patients with an H3K27M-mutant DNMG and reviewed previously reported cases.Among 51 patients (18 children and 33 adults) diagnosed with an H3K27M diffuse glioma, we identified two patients (4%) who had a non-midline location. Including our two patients, 39 patients were reported in the literature with an H3K27M-mutant DNMG. Tumors were most frequently located in the temporal lobe (48%), affected adolescents and adults, and were associated with a poor outcome (median overall survival was 10.3 months (0.1-84)). Median age at diagnosis was 19.1 years. Tumors frequently harbored TP53 mutations (74%), ATRX mutations (71%) and PDGFRA mutations or amplifications (44%). In DNA methylation analysis, H3K27M-mutant DNMG clustered within or close to the reference group of H3K27M-mutant DMG. Compared to their midline counterpart, non-midline gliomas with H3K27M mutations seemed more frequently associated with PDGFRA alterations.DNMG with H3K27M mutations share many similarities with their midline counterpart, suggesting that they correspond to a rare anatomical presentation of these tumors. This is of paramount importance, as they may benefit from new therapeutic approaches such as ONC201.

Keyword(s): Diffuse intrinsic pontine glioma ; Diffuse midline glioma H3 K27-altered ; H3K27M ; H3K28M ; Methylation ; Non-midline ; Pediatric glioma

Note: 2024 Sep;169(2):391-398

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Contributing Institute(s):

1. Pädiatrische Gliomforschung (B360)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; DEAL Springer ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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