Characteristics of H3K27M-mutant diffuse gliomas with a non-midline location.

Diffuse intrinsic pontine glioma Diffuse midline glioma H3 K27-altered H3K27M H3K28M Methylation Non-midline Pediatric glioma

Journal

Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335

Informations de publication

Date de publication:
27 Jun 2024
Historique:
received: 02 05 2024
accepted: 31 05 2024
medline: 28 6 2024
pubmed: 28 6 2024
entrez: 27 6 2024
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 38937309
doi: 10.1007/s11060-024-04733-z
pii: 10.1007/s11060-024-04733-z
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Souhir Guidara (S)

Department of Medical Genetics, Hedi Chaker Hospital, Sfax, Tunisia. souhir.guidara89@gmail.com.

Antoine Seyve (A)

Department of Neurooncology, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.

Delphine Poncet (D)

Department of Pathology, Groupe Hospitalier Est, Hospices Civils de Lyon, Bron, France.
Institut Neuro Myo Gène (INMG), Pathophysiology and Genetics of Neuron and Muscle (PGNM), Université Claude Bernard Lyon 1, CNRS UMR 5261-INSERM U1315, Neuron-Muscle interaction team, Lyon, France.

Camille Leonce (C)

Department of Pathology, Groupe Hospitalier Est, Hospices Civils de Lyon, Bron, France.
Centre Léon Bérard, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Lyon, France.

Pierre-Paul Bringuier (PP)

Department of Pathology, Groupe Hospitalier Est, Hospices Civils de Lyon, Bron, France.
Université Claude Bernard Lyon 1, Villeurbanne, France.

Anne McLeer (A)

Service d'Anatomie et Cytologie Pathologiques CHU Grenoble Alpes, Institute for Advanced Biosciences UGA, Université Grenoble Alpes, INSERM U1209/CNRS 5309, Grenoble, France.

Dominik Sturm (D)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Stéphanie Cartalat (S)

Department of Neurooncology, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.

Thiebaud Picart (T)

Centre Léon Bérard, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Lyon, France.
Université Claude Bernard Lyon 1, Villeurbanne, France.
Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.

Anthony Ferrari (A)

Gilles Thomas Bioinformatics Platform, Synergie Lyon Cancer, Cancer Research Center of Lyon, Centre Léon Bérard FR, Lyon, France.

Jürgen Hench (J)

Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.

Stephan Frank (S)

Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.

David Meyronet (D)

Department of Pathology, Groupe Hospitalier Est, Hospices Civils de Lyon, Bron, France.
Université Claude Bernard Lyon 1, Villeurbanne, France.
Cancer Initiation and Tumoral Cell Identity Department, Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, Lyon, France.

François Ducray (F)

Department of Neurooncology, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.
Université Claude Bernard Lyon 1, Villeurbanne, France.
Cancer Initiation and Tumoral Cell Identity Department, Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, Lyon, France.

Marc Barritault (M)

Department of Pathology, Groupe Hospitalier Est, Hospices Civils de Lyon, Bron, France. marc.barritault@chu-lyon.fr.
Cancer Initiation and Tumoral Cell Identity Department, Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, Lyon, France. marc.barritault@chu-lyon.fr.

Classifications MeSH