Diffuse Midline Glioma, H3 K27-Altered

1. Disease Information

1.1 Concise overview

Diffuse midline glioma, H3 K27-altered is an infiltrative midline glioma defined by H3K27-pathway disruption (loss of H3K27 trimethylation) and is assigned CNS WHO grade 4 regardless of histologic features. It most commonly arises in midline CNS structures such as the pons/brainstem (historically “DIPG”), thalamus, and spinal cord and carries a poor prognosis, especially in children. (park2023the2021who pages 2-2, park2023the2021who pages 6-7, vallero2023pediatricdiffusemidline pages 2-3)

1.2 Key identifiers and ontology mapping

• MONDO: MONDO:1060171 (vallero2023pediatricdiffusemidline pages 2-3)
• WHO CNS classification: WHO CNS5 (2021), pediatric-type diffuse high-grade glioma family; DMG, H3 K27-altered is a tumor type within this family (gianno2022paediatrictypediffusehighgrade pages 1-2)
• Diagnostic molecular criteria (WHO CNS5-aligned): midline location plus H3 K27M mutation OR EZHIP overexpression OR EGFR alteration → “diffuse midline glioma, H3 K27-altered” (park2023the2021who pages 2-2)

Not retrieved in this tool session: ICD-10/ICD-11 codes, MeSH IDs, Orphanet IDs, OMIM disease entry IDs. These may exist but were not present in the provided full-text evidence chunks.

1.3 Common synonyms / alternative names

• “Diffuse midline glioma, H3 K27M-mutant” (WHO 2016 name)
• “Diffuse intrinsic pontine glioma (DIPG)” (clinical/radiologic term for pontine cases)
• “H3K27-altered diffuse midline glioma” (wisniewski2023h3k27maltereddiffuse pages 1-3, vallero2023pediatricdiffusemidline pages 2-3)

1.4 Evidence source types

The synthesis below is derived from aggregated resources: multicenter and single-center retrospective cohorts, systematic reviews, and contemporary narrative reviews, plus trial registry entries (ClinicalTrials.gov). (hayashi2024neuroradiologicalgeneticand pages 1-2, damodharan2023molecularcharacterizationand pages 1-2, NCT04808245 chunk 1, NCT04196413 chunk 2)

Table: This table summarizes the core identifiers, nomenclature changes, WHO CNS5 diagnostic criteria, synonyms, and typical anatomical sites for diffuse midline glioma, H3 K27-altered. It is useful as a compact reference for disease ontology and naming normalization in a knowledge base.

2. Etiology

2.1 Primary causal factors

DMG, H3 K27-altered is primarily driven by somatic alterations affecting histone H3 lysine-27 regulation, most commonly a K27M missense substitution in histone H3 genes, leading to epigenetic dysregulation. (mandorino2024pediatricdiffusemidline pages 1-2, gue2024the2021world pages 15-16)

2.2 Risk factors

• Genetic risk factors (germline): No consistent inherited causal variants were identified in the retrieved sources; the defining events are described as tumor somatic alterations. (mandorino2024pediatricdiffusemidline pages 1-2, gue2024the2021world pages 15-16)
• Environmental risk factors: No specific environmental exposures were identified in the retrieved evidence.

2.3 Protective factors

No validated protective factors (genetic or environmental) were identified in the retrieved evidence.

2.4 Gene–environment interactions

No gene–environment interaction evidence was identified in the retrieved sources.

3. Phenotypes

3.1 Core clinical phenotype (especially pontine/brainstem cases)

A common presentation—classically described for DIPG/brainstem DMG—includes cranial neuropathies, long-tract (pyramidal) signs, and ataxia. Vallero et al. additionally specify long-tract findings such as hyperreflexia, clonus, increased tone, and Babinski sign. (vallero2023pediatricdiffusemidline pages 2-3, broggi2024clinico–pathologicalfeaturesof pages 1-2)

Mandorino et al. (2024) highlight pediatric presentations including coordination problems, limb weakness, speech difficulties, and vision impairment. (mandorino2024pediatricdiffusemidline pages 1-2)

3.2 Age of onset and course

• Predominantly a pediatric disease; pediatric DMG/DIPG often affects children in early childhood/school age (e.g., 4–9 years in one review). (mandorino2024pediatricdiffusemidline pages 1-2, vallero2023pediatricdiffusemidline pages 2-3)
• Adults are also affected, with adult cohorts showing frequent thalamic involvement and longer median survival than historical pediatric cohorts. (schulte2020clinicalradiologicand pages 1-2, broggi2024clinico–pathologicalfeaturesof pages 1-2)

3.3 Suggested HPO mappings

Table: This table summarizes the characteristic clinical presentation of diffuse midline glioma, H3 K27-altered, including the classic DIPG triad and other common symptoms, with suggested HPO mappings. It is useful for phenotype curation and disease knowledge base annotation.

3.4 Quality-of-life impact

Neurologic deficits (ataxia, cranial nerve palsies, long-tract signs/weakness) directly impair gait, speech, vision, and daily function; radiotherapy is used palliatively to reduce symptoms but does not cure disease. (vallero2023pediatricdiffusemidline pages 2-3, mandorino2024pediatricdiffusemidline pages 1-2)

4. Genetic / Molecular Information

4.1 Causal genes and defining alterations

WHO CNS5 recognizes DMG, H3 K27-altered as defined by H3 K27M mutation, or alternative molecular mechanisms including EZHIP overexpression or EGFR alteration, all producing loss of H3K27 methylation. (park2023the2021who pages 2-2, gue2024the2021world pages 15-16, park2023the2021who pages 6-7)

A review definition consistent with WHO CNS5 is quoted as: “An infiltrative midline glioma with loss of H3 p.K28me3 (K27me3) and either … p.K28M (K27M) … aberrant overexpression of EZHIP, or an EGFR mutation (CNS WHO grade 4).” (wisniewski2023h3k27maltereddiffuse pages 1-3)

4.2 Frequencies of major alterations (selected cohorts)

• Pediatric/combined cohorts: Dufour et al. report H3F3A K27M ~63.6% and HIST1H3B K27M ~15.9% among interpretable tumors; ~20.5% were histone wild-type in their cohort. (dufour2020identificationofprognostic pages 8-10)
• Kansai multicenter cohort (n=93 DMG): MGMT promoter methylation 9%, FGFR1 mutation 14%, EGFR mutation 3%, TERT promoter mutation 3%, BRAF V600E 1%, HIST1H3B K27M 2%. (hayashi2024neuroradiologicalgeneticand pages 1-2)

4.3 Prognostic molecular markers

• TP53 alteration/p53 overexpression is repeatedly associated with worse outcomes (damodharan2023molecularcharacterizationand pages 1-2, wang2021clinicalfeaturesand pages 3-4)
• PDGFRA amplification, 17p loss, and complex chromosomal profiles were associated with worse survival in a pediatric cohort. (dufour2020identificationofprognostic pages 8-10)
• MGMT promoter methylation is uncommon and was not associated with OS in an adult cohort analysis; this supports the concept that temozolomide benefit may be limited in many cases. (gong2023differencesinsurvival pages 7-9, hayashi2024neuroradiologicalgeneticand pages 1-2)

Table: This table summarizes major molecular alterations reported in diffuse midline glioma, H3 K27-altered, with representative frequencies and prognostic associations across key pediatric, adult, and multicenter cohorts. It is useful for comparing defining drivers, recurrent co-alterations, and biomarkers linked to survival.

5. Environmental Information

No validated environmental, lifestyle, or infectious causal factors were identified in the retrieved evidence. The disease definition and therapeutic strategies in these sources center on tumor-intrinsic somatic alterations and local CNS anatomy. (mandorino2024pediatricdiffusemidline pages 1-2, gue2024the2021world pages 15-16)

6. Mechanism / Pathophysiology

6.1 Core epigenetic mechanism

H3 K27 alterations (e.g., K27M) and EZHIP overexpression converge on polycomb repressive complex 2 (PRC2) interference, producing global reduction of H3K27me2/H3K27me3 and widespread gene-expression dysregulation that supports aggressive glioma biology. (gue2024the2021world pages 15-16)

6.2 Causal chain (simplified)

1. Somatic H3K27-pathway alteration (H3 K27M, EZHIP overexpression, or EGFR-altered subtype) (park2023the2021who pages 2-2, gue2024the2021world pages 15-16)
2. Loss of H3K27me3 and altered chromatin states → abnormal transcriptional programs (gue2024the2021world pages 15-16)
3. Infiltrative glioma growth in critical midline structures (pons/thalamus/spinal cord) (vallero2023pediatricdiffusemidline pages 2-3, schulte2020clinicalradiologicand pages 1-2)
4. Neurologic deficits from local tract/nuclei involvement (cranial nerves, corticospinal tracts, cerebellar pathways) leading to the classic phenotype triad and progressive disability (vallero2023pediatricdiffusemidline pages 2-3, broggi2024clinico–pathologicalfeaturesof pages 1-2)

6.3 Pathways and processes (ontology suggestions)

• GO Biological Process (suggested): chromatin organization; histone H3-K27 methylation; negative regulation of gene expression (epigenetic); gliogenesis; regulation of cell proliferation.
• GO Cellular Component (suggested): Polycomb repressive complex 2 (PRC2); nucleosome; chromatin.
• Cell types (CL, suggested): astrocyte (astrocytic lineage tumor); oligodendrocyte precursor cell / glial progenitor-like states are commonly discussed in DMG biology (not quantitatively detailed in retrieved excerpts).

6.4 Advanced profiling (single-cell/spatial/multi-omics)

The retrieved evidence set emphasizes molecular profiling via biopsy/NGS and methylation profiling, but does not provide detailed single-cell or spatial transcriptomics results in the accessible excerpts. (nonnenbroich2024h3k27altereddiffusemidline pages 1-2)

7. Anatomical Structures Affected

7.1 Organ/tissue localization

Primary involvement is the central nervous system, particularly midline structures: - Brainstem/pons (classic DIPG) - Thalamus - Spinal cord (vallero2023pediatricdiffusemidline pages 2-3, schulte2020clinicalradiologicand pages 1-2, hayashi2024neuroradiologicalgeneticand pages 1-2)

7.2 Suggested UBERON mappings

• Pons (UBERON:0000988)
• Thalamus (UBERON:0001897)
• Spinal cord (UBERON:0002240)

8. Temporal Development

8.1 Onset and progression

Disease is typically subacute to progressive with rapid neurologic decline reflecting infiltrative growth in critical midline structures. Pediatric presentations are common; adult presentations occur and may have different site distribution and outcomes. (mandorino2024pediatricdiffusemidline pages 1-2, schulte2020clinicalradiologicand pages 1-2)

8.2 Staging

No formal staging system specific to DMG was identified in the retrieved evidence; clinically, course is commonly framed as diagnosis → post-radiotherapy period → progression/recurrence, with consideration of re-irradiation at recurrence. (vallero2023pediatricdiffusemidline pages 2-3, damodharan2023molecularcharacterizationand pages 1-2)

9. Inheritance and Population

9.1 Epidemiology

• Vallero et al. summarize pediatric burden as ~20% of pediatric CNS tumors with ~200–300 new cases/year in the United States (as reported in their review context). (vallero2023pediatricdiffusemidline pages 2-3)
• An adult-focused review cites incidence around 2.32 cases per 1 million persons/year in adults (>20 years). (broggi2024clinico–pathologicalfeaturesof pages 1-2)

9.2 Inheritance

This is not typically a Mendelian inherited disorder; it is defined by tumor somatic alterations. No penetrance/carrier frequency/founder-effect data were identified in the retrieved evidence.

10. Diagnostics

10.1 Imaging

MRI is widely described as the diagnostic gold standard for pontine/brainstem cases; Vallero et al. note typical DIPG imaging criteria such as a lesion involving >50% of the pons. (vallero2023pediatricdiffusemidline pages 2-3)

10.2 Tissue diagnosis and molecular confirmation

• Biopsy in brainstem lesions has historically been debated, but multiple sources describe a trend toward stereotactic biopsy to enable immunohistochemistry and molecular profiling (NGS, methylation profiling). (vallero2023pediatricdiffusemidline pages 2-3, nonnenbroich2024h3k27altereddiffusemidline pages 1-2, damodharan2023molecularcharacterizationand pages 1-2)
• WHO-aligned pathologic workup commonly includes IHC for H3 K27M and assessment of H3K27me3 loss, with EZHIP evaluation where relevant; strong diffuse H3 K27M immunoreactivity with H3K27me3 loss supports diagnosis. (broggi2024clinico–pathologicalfeaturesof pages 1-2)

10.3 Differential diagnosis (high level)

Midline gliomas without H3 K27 alteration and other pediatric high-grade gliomas (e.g., hemispheric H3 G34-mutant tumors) are key considerations in the modern WHO framework. (park2023the2021who pages 2-2)

11. Outcome / Prognosis

11.1 Survival statistics (selected recent/large cohorts)

• Kansai multicenter cohort (n=93, 24 hospitals): median PFS 9.9 months and median OS 16.6 months (hayashi2024neuroradiologicalgeneticand pages 1-2). The Kaplan–Meier figure region containing these medians is shown in the extracted survival-curve images. (hayashi2024neuroradiologicalgeneticand media dec99d06, hayashi2024neuroradiologicalgeneticand media 8f7749a2, hayashi2024neuroradiologicalgeneticand media 14f6a8a7)
• Adult cohort (n=60): OS reported as 27.6 months in Schulte et al. (schulte2020clinicalradiologicand pages 1-2, schulte2020clinicalradiologicand pages 7-8)
• Mixed-age cohort (n=43): median OS 12.83 months with 12- and 24-month OS rates 53.8% and 40.2%, respectively. (wang2021clinicalfeaturesand pages 3-4)
• Reviews emphasize poor pediatric prognosis with survival often around 12 months and very low long-term survival. (mandorino2024pediatricdiffusemidline pages 1-2)

11.2 Prognostic factors (clinical)

• Performance status (KPS) is repeatedly prognostic; KPS ≥80 (Kansai cohort) and KPS ≥70 (Wang cohort) are associated with improved OS. (hayashi2024neuroradiologicalgeneticand pages 1-2, wang2021clinicalfeaturesand pages 3-4)
• Adjuvant radiotherapy and chemoradiotherapy are associated with improved OS in retrospective analyses. (wang2021clinicalfeaturesand pages 3-4, gong2023differencesinsurvival pages 7-9)

12. Treatment

12.1 Standard of care / real-world implementation

Radiotherapy remains the principal standard palliative treatment, with typical fractionated dosing in the ~54–60 Gy range (Vallero) and 59 Gy cited in a pediatric review context. (vallero2023pediatricdiffusemidline pages 2-3, mandorino2024pediatricdiffusemidline pages 1-2)

Real-world practice patterns from the Kansai multicenter cohort (n=93) include: - Resection (when feasible) in 36% - Adjuvant radiation + chemotherapy in 83% - Temozolomide use in 76% - Bevacizumab use in 42% (hayashi2024neuroradiologicalgeneticand pages 1-2)

Damodharan et al. (2023) systematic review of individual participant trial data highlights that re-irradiation was the only statistically significant modality associated with survival benefit in their pooled analysis. (damodharan2023molecularcharacterizationand pages 1-2)

12.2 Emerging therapies (2023–2024 prioritized)

• Imipridones / ONC201-class agents: Recent reviews summarize multiple clinical datasets with median OS values around ~16–22 months depending on cohort and timing, and emphasize earlier post-radiotherapy administration as potentially beneficial. (nonnenbroich2024h3k27altereddiffusemidline pages 4-6, yang2024newprogressin pages 3-5)
• Epigenetic therapies (HDAC inhibition): panobinostat continues to be studied, including approaches to improve delivery such as convection-enhanced delivery (CED). (rechberger2023benchtobedsideinvestigationsof pages 13-15, nonnenbroich2024h3k27altereddiffusemidline pages 9-10)
• Cellular immunotherapy and vaccines: Multiple active trials target H3K27M neoantigens (vaccine or engineered effector cells) and GD2 CAR-T approaches. (NCT04808245 chunk 1, NCT04196413 chunk 2, NCT07501156 chunk 1)

MAXO (suggested) intervention terms (high-level, for KB annotation): external beam radiotherapy; stereotactic biopsy; chemotherapy; immunotherapy; CAR T-cell therapy; peptide vaccination; re-irradiation; convection-enhanced delivery.

12.3 Key clinical trials (ClinicalTrials.gov)

Table: This table summarizes key current and emerging ClinicalTrials.gov studies for diffuse midline glioma, H3 K27-altered, spanning CAR-T, peptide vaccination, radiation strategy, HDAC inhibition, and engineered immune effector cell approaches. It is useful for quickly comparing mechanism, eligibility, route, endpoints, and recruitment status across major active protocols.

13. Prevention

No established primary prevention strategies are supported by the retrieved evidence, consistent with a disease primarily driven by sporadic somatic alterations and presenting as a rare CNS tumor. Secondary prevention (screening) is not established; diagnosis is typically symptom- and imaging-driven. (mandorino2024pediatricdiffusemidline pages 1-2, vallero2023pediatricdiffusemidline pages 2-3)

14. Other Species / Natural Disease

No naturally occurring veterinary analogs were identified in the retrieved evidence.

15. Model Organisms

The retrieved evidence set references preclinical models (e.g., murine models used to test epigenetic combinations) but does not provide detailed, model-by-model phenotype recapitulation in the accessible excerpts. (nonnenbroich2024h3k27altereddiffusemidline pages 4-6)

Expert opinions / analysis (authoritative sources)

• Contemporary expert reviews emphasize that despite extensive clinical trial activity, radiotherapy remains the only proven standard, and progress likely requires combination therapies, improved delivery across the BBB/BBTB, and molecularly guided strategies. (nonnenbroich2024h3k27altereddiffusemidline pages 1-2, nonnenbroich2024h3k27altereddiffusemidline pages 9-10)
• Drug-delivery concepts such as maximizing “drug–tumor residence time” and focusing on combinational regimens are emphasized as necessary to overcome resistance and clearance limitations. (rechberger2023benchtobedsideinvestigationsof pages 13-15)

Notes on PMID availability

The provided full-text evidence chunks and trial registry records include DOI URLs and publication months/years but did not include PMIDs for most articles. Where PMID is required for downstream normalization, the DOI URLs provided here can be used to programmatically map to PubMed records.

References

1. (vallero2023pediatricdiffusemidline pages 2-3): Stefano Gabriele Vallero, Luca Bertero, Giovanni Morana, Paola Sciortino, Daniele Bertin, Anna Mussano, Federica Silvia Ricci, Paola Peretta, and Franca Fagioli. Pediatric diffuse midline glioma h3k27- altered: a complex clinical and biological landscape behind a neatly defined tumor type. Frontiers in Oncology, Jan 2023. URL: https://doi.org/10.3389/fonc.2022.1082062, doi:10.3389/fonc.2022.1082062. This article has 62 citations.

2. (gianno2022paediatrictypediffusehighgrade pages 1-2): Francesca Gianno, Isabella Giovannoni, Barbara Cafferata, Francesca Diomedi-Camassei, Simone Minasi, Sabina Barresi, Francesca Romana Buttarelli, Viola Alesi, Antonello Cardoni, Manila Antonelli, Chiara Puggioni, Giovanna Stefania Colafati, Andrea Carai, Maria Vinci, Angela Mastronuzzi, Evelina Miele, Rita Alaggio, Felice Giangaspero, and Sabrina Rossi. Paediatric-type diffuse high-grade gliomas in the 5th cns who classification. Pathologica, 114:422-435, Dec 2022. URL: https://doi.org/10.32074/1591-951x-830, doi:10.32074/1591-951x-830. This article has 66 citations.

3. (schulte2020clinicalradiologicand pages 1-2): Jessica D Schulte, Robin A Buerki, Sarah Lapointe, Annette M Molinaro, Yalan Zhang, Javier E Villanueva-Meyer, Arie Perry, Joanna J Phillips, Tarik Tihan, Andrew W Bollen, Melike Pekmezci, Nicholas Butowski, Nancy Ann Oberheim Bush, Jennie W Taylor, Susan M Chang, Philip Theodosopoulos, Manish K Aghi, Shawn L Hervey-Jumper, Mitchel S Berger, David A Solomon, and Jennifer L Clarke. Clinical, radiologic, and genetic characteristics of histone h3 k27m-mutant diffuse midline gliomas in adults. Neuro-oncology Advances, Oct 2020. URL: https://doi.org/10.1093/noajnl/vdaa142, doi:10.1093/noajnl/vdaa142. This article has 124 citations and is from a peer-reviewed journal.

4. (park2023the2021who pages 2-2): Yae Won Park, Philipp Vollmuth, Martha Foltyn‐Dumitru, Felix Sahm, Sung Soo Ahn, Jong Hee Chang, and Se Hoon Kim. The 2021 who classification for gliomas and implications on imaging diagnosis: part 2—summary of imaging findings on pediatric‐type diffuse high‐grade gliomas, pediatric‐type diffuse low‐grade gliomas, and circumscribed astrocytic gliomas. Journal of Magnetic Resonance Imaging, 58:690-708, Apr 2023. URL: https://doi.org/10.1002/jmri.28740, doi:10.1002/jmri.28740. This article has 48 citations and is from a domain leading peer-reviewed journal.

5. (park2023the2021who pages 6-7): Yae Won Park, Philipp Vollmuth, Martha Foltyn‐Dumitru, Felix Sahm, Sung Soo Ahn, Jong Hee Chang, and Se Hoon Kim. The 2021 who classification for gliomas and implications on imaging diagnosis: part 2—summary of imaging findings on pediatric‐type diffuse high‐grade gliomas, pediatric‐type diffuse low‐grade gliomas, and circumscribed astrocytic gliomas. Journal of Magnetic Resonance Imaging, 58:690-708, Apr 2023. URL: https://doi.org/10.1002/jmri.28740, doi:10.1002/jmri.28740. This article has 48 citations and is from a domain leading peer-reviewed journal.

6. (wisniewski2023h3k27maltereddiffuse pages 1-3): Karol Wiśniewski, Andrew Ghaly, Kate Drummond, and Andreas Fahlstrӧm. H3 k27m-altered diffuse midline gliomas: a review. Indian Journal of Neurosurgery, 12:104-115, Jul 2023. URL: https://doi.org/10.1055/s-0043-1771192, doi:10.1055/s-0043-1771192. This article has 9 citations.

7. (hayashi2024neuroradiologicalgeneticand pages 1-2): Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano, Daisuke Sakamoto, Tomoko Iida, Yoshiki Arakawa, Takeshi Kawauchi, Yukihiko Sonoda, Yuta Mitobe, Kenichi Ishibashi, Masahide Matsuda, Takamune Achiha, Takahiro Tomita, Masahiro Nonaka, Keijiro Hara, Noriyoshi Takebe, Takashi Tsuzuki, Yoshikazu Nakajima, Shiro Ohue, Nobuyuki Nakajima, Akira Watanabe, Akihiro Inoue, Masao Umegaki, Daisuke Kanematsu, Asako Katsuma, Miho Sumida, Tomoko Shofuda, Masayuki Mano, Manabu Kinoshita, Kanji Mori, Naoyuki Nakao, and Yonehiro Kanemura. Neuroradiological, genetic and clinical characteristics of histone h3 k27-mutant diffuse midline gliomas in the kansai molecular diagnosis network for cns tumors (kansai network): multicenter retrospective cohort. Acta Neuropathologica Communications, Jul 2024. URL: https://doi.org/10.1186/s40478-024-01808-w, doi:10.1186/s40478-024-01808-w. This article has 4 citations and is from a peer-reviewed journal.

8. (damodharan2023molecularcharacterizationand pages 1-2): Sudarshawn Damodharan, Alexandra Abbott, Kaitlyn Kellar, Qianqian Zhao, and Mahua Dey. Molecular characterization and treatment approaches for pediatric h3 k27-altered diffuse midline glioma: integrated systematic review of individual clinical trial participant data. Cancers, 15:3478, Jul 2023. URL: https://doi.org/10.3390/cancers15133478, doi:10.3390/cancers15133478. This article has 7 citations.

9. (NCT04808245 chunk 1): A MultIceNTER Phase I Peptide VaCcine Trial for the Treatment of H3-Mutated Gliomas. German Cancer Research Center. 2023. ClinicalTrials.gov Identifier: NCT04808245

10. (NCT04196413 chunk 2): GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas (DIPG) & Spinal Diffuse Midline Glioma(DMG). Stanford University. 2020. ClinicalTrials.gov Identifier: NCT04196413

11. (gue2024the2021world pages 15-16): Racine Gue and Dhairya A. Lakhani. The 2021 world health organization central nervous system tumor classification: the spectrum of diffuse gliomas. Biomedicines, 12:1349, Jun 2024. URL: https://doi.org/10.3390/biomedicines12061349, doi:10.3390/biomedicines12061349. This article has 13 citations.

12. (broggi2024clinico–pathologicalfeaturesof pages 1-2): Giuseppe Broggi, Serena Salzano, Maria Failla, Giuseppe Maria Vincenzo Barbagallo, Francesco Certo, Magda Zanelli, Andrea Palicelli, Maurizio Zizzo, Nektarios Koufopoulos, Gaetano Magro, and Rosario Caltabiano. Clinico–pathological features of diffuse midline glioma, h3 k27-altered in adults: a comprehensive review of the literature with an additional single-institution case series. Diagnostics, 14:2617, Nov 2024. URL: https://doi.org/10.3390/diagnostics14232617, doi:10.3390/diagnostics14232617. This article has 7 citations.

13. (nonnenbroich2024h3k27altereddiffusemidline pages 1-2): Leo F. Nonnenbroich, Samantha M. Bouchal, Elena Millesi, Julian S. Rechberger, Soumen Khatua, and David J. Daniels. H3k27-altered diffuse midline glioma of the brainstem: from molecular mechanisms to targeted interventions. Cells, 13:1122, Jun 2024. URL: https://doi.org/10.3390/cells13131122, doi:10.3390/cells13131122. This article has 14 citations.

14. (park2023the2021who pages 7-7): Yae Won Park, Philipp Vollmuth, Martha Foltyn‐Dumitru, Felix Sahm, Sung Soo Ahn, Jong Hee Chang, and Se Hoon Kim. The 2021 who classification for gliomas and implications on imaging diagnosis: part 2—summary of imaging findings on pediatric‐type diffuse high‐grade gliomas, pediatric‐type diffuse low‐grade gliomas, and circumscribed astrocytic gliomas. Journal of Magnetic Resonance Imaging, 58:690-708, Apr 2023. URL: https://doi.org/10.1002/jmri.28740, doi:10.1002/jmri.28740. This article has 48 citations and is from a domain leading peer-reviewed journal.

15. (mandorino2024pediatricdiffusemidline pages 1-2): Manuela Mandorino, Ahana Maitra, Domenico Armenise, Olga Maria Baldelli, Morena Miciaccia, Savina Ferorelli, Maria Grazia Perrone, and Antonio Scilimati. Pediatric diffuse midline glioma h3k27-altered: from developmental origins to therapeutic challenges. Cancers, 16:1814, May 2024. URL: https://doi.org/10.3390/cancers16101814, doi:10.3390/cancers16101814. This article has 21 citations.

16. (dufour2020identificationofprognostic pages 8-10): Charlotte Dufour, Romain Perbet, Pierre Leblond, Romain Vasseur, Laurence Stechly, Adeline Pierache, Nicolas Reyns, Gustavo Touzet, Emilie Le Rhun, Matthieu Vinchon, Claude‐Alain Maurage, Fabienne Escande, and Florence Renaud. Identification of prognostic markers in diffuse midline gliomas h3k27m‐mutant. Brain Pathology, 30:179-190, Aug 2020. URL: https://doi.org/10.1111/bpa.12768, doi:10.1111/bpa.12768. This article has 40 citations and is from a domain leading peer-reviewed journal.

17. (wang2021clinicalfeaturesand pages 3-4): Yuan Wang, Lan-lan Feng, Pei-gang Ji, Jing-hui Liu, Shao-chun Guo, Yu-long Zhai, Eric W. Sankey, Yue Wang, Yan-rong Xue, Na Wang, Miao Lou, Meng Xu, Min Chao, Guo-Dong Gao, Yan Qu, Li Gong, and Liang Wang. Clinical features and molecular markers on diffuse midline gliomas with h3k27m mutations: a 43 cases retrospective cohort study. Frontiers in Oncology, Feb 2021. URL: https://doi.org/10.3389/fonc.2020.602553, doi:10.3389/fonc.2020.602553. This article has 48 citations.

18. (gong2023differencesinsurvival pages 7-9): Xuan Gong, S. Kuang, Dong-feng Deng, Jun Wu, Longbo Zhang, and Chaoyuan Liu. Differences in survival prognosticators between children and adults with h3k27m‐mutant diffuse midline glioma. CNS Neuroscience & Therapeutics, 29:3863-3875, Jun 2023. URL: https://doi.org/10.1111/cns.14307, doi:10.1111/cns.14307. This article has 17 citations and is from a peer-reviewed journal.

19. (hayashi2024neuroradiologicalgeneticand media dec99d06): Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano, Daisuke Sakamoto, Tomoko Iida, Yoshiki Arakawa, Takeshi Kawauchi, Yukihiko Sonoda, Yuta Mitobe, Kenichi Ishibashi, Masahide Matsuda, Takamune Achiha, Takahiro Tomita, Masahiro Nonaka, Keijiro Hara, Noriyoshi Takebe, Takashi Tsuzuki, Yoshikazu Nakajima, Shiro Ohue, Nobuyuki Nakajima, Akira Watanabe, Akihiro Inoue, Masao Umegaki, Daisuke Kanematsu, Asako Katsuma, Miho Sumida, Tomoko Shofuda, Masayuki Mano, Manabu Kinoshita, Kanji Mori, Naoyuki Nakao, and Yonehiro Kanemura. Neuroradiological, genetic and clinical characteristics of histone h3 k27-mutant diffuse midline gliomas in the kansai molecular diagnosis network for cns tumors (kansai network): multicenter retrospective cohort. Acta Neuropathologica Communications, Jul 2024. URL: https://doi.org/10.1186/s40478-024-01808-w, doi:10.1186/s40478-024-01808-w. This article has 4 citations and is from a peer-reviewed journal.

20. (hayashi2024neuroradiologicalgeneticand media 8f7749a2): Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano, Daisuke Sakamoto, Tomoko Iida, Yoshiki Arakawa, Takeshi Kawauchi, Yukihiko Sonoda, Yuta Mitobe, Kenichi Ishibashi, Masahide Matsuda, Takamune Achiha, Takahiro Tomita, Masahiro Nonaka, Keijiro Hara, Noriyoshi Takebe, Takashi Tsuzuki, Yoshikazu Nakajima, Shiro Ohue, Nobuyuki Nakajima, Akira Watanabe, Akihiro Inoue, Masao Umegaki, Daisuke Kanematsu, Asako Katsuma, Miho Sumida, Tomoko Shofuda, Masayuki Mano, Manabu Kinoshita, Kanji Mori, Naoyuki Nakao, and Yonehiro Kanemura. Neuroradiological, genetic and clinical characteristics of histone h3 k27-mutant diffuse midline gliomas in the kansai molecular diagnosis network for cns tumors (kansai network): multicenter retrospective cohort. Acta Neuropathologica Communications, Jul 2024. URL: https://doi.org/10.1186/s40478-024-01808-w, doi:10.1186/s40478-024-01808-w. This article has 4 citations and is from a peer-reviewed journal.

21. (hayashi2024neuroradiologicalgeneticand media 14f6a8a7): Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano, Daisuke Sakamoto, Tomoko Iida, Yoshiki Arakawa, Takeshi Kawauchi, Yukihiko Sonoda, Yuta Mitobe, Kenichi Ishibashi, Masahide Matsuda, Takamune Achiha, Takahiro Tomita, Masahiro Nonaka, Keijiro Hara, Noriyoshi Takebe, Takashi Tsuzuki, Yoshikazu Nakajima, Shiro Ohue, Nobuyuki Nakajima, Akira Watanabe, Akihiro Inoue, Masao Umegaki, Daisuke Kanematsu, Asako Katsuma, Miho Sumida, Tomoko Shofuda, Masayuki Mano, Manabu Kinoshita, Kanji Mori, Naoyuki Nakao, and Yonehiro Kanemura. Neuroradiological, genetic and clinical characteristics of histone h3 k27-mutant diffuse midline gliomas in the kansai molecular diagnosis network for cns tumors (kansai network): multicenter retrospective cohort. Acta Neuropathologica Communications, Jul 2024. URL: https://doi.org/10.1186/s40478-024-01808-w, doi:10.1186/s40478-024-01808-w. This article has 4 citations and is from a peer-reviewed journal.

22. (schulte2020clinicalradiologicand pages 7-8): Jessica D Schulte, Robin A Buerki, Sarah Lapointe, Annette M Molinaro, Yalan Zhang, Javier E Villanueva-Meyer, Arie Perry, Joanna J Phillips, Tarik Tihan, Andrew W Bollen, Melike Pekmezci, Nicholas Butowski, Nancy Ann Oberheim Bush, Jennie W Taylor, Susan M Chang, Philip Theodosopoulos, Manish K Aghi, Shawn L Hervey-Jumper, Mitchel S Berger, David A Solomon, and Jennifer L Clarke. Clinical, radiologic, and genetic characteristics of histone h3 k27m-mutant diffuse midline gliomas in adults. Neuro-oncology Advances, Oct 2020. URL: https://doi.org/10.1093/noajnl/vdaa142, doi:10.1093/noajnl/vdaa142. This article has 124 citations and is from a peer-reviewed journal.

23. (nonnenbroich2024h3k27altereddiffusemidline pages 4-6): Leo F. Nonnenbroich, Samantha M. Bouchal, Elena Millesi, Julian S. Rechberger, Soumen Khatua, and David J. Daniels. H3k27-altered diffuse midline glioma of the brainstem: from molecular mechanisms to targeted interventions. Cells, 13:1122, Jun 2024. URL: https://doi.org/10.3390/cells13131122, doi:10.3390/cells13131122. This article has 14 citations.

24. (yang2024newprogressin pages 3-5): Zhi Yang, Liang Sun, Haibin Chen, Caixing Sun, and Liang Xia. New progress in the treatment of diffuse midline glioma with h3k27m alteration. Heliyon, 10:e24877, Jan 2024. URL: https://doi.org/10.1016/j.heliyon.2024.e24877, doi:10.1016/j.heliyon.2024.e24877. This article has 11 citations.

25. (rechberger2023benchtobedsideinvestigationsof pages 13-15): Julian S. Rechberger, Samantha M. Bouchal, Erica A. Power, Leo F. Nonnenbroich, Cody L. Nesvick, and David J. Daniels. Bench-to-bedside investigations of h3 k27-altered diffuse midline glioma: drug targets and potential pharmacotherapies. Expert Opinion on Therapeutic Targets, 27:1071-1086, Nov 2023. URL: https://doi.org/10.1080/14728222.2023.2277232, doi:10.1080/14728222.2023.2277232. This article has 5 citations and is from a peer-reviewed journal.

26. (nonnenbroich2024h3k27altereddiffusemidline pages 9-10): Leo F. Nonnenbroich, Samantha M. Bouchal, Elena Millesi, Julian S. Rechberger, Soumen Khatua, and David J. Daniels. H3k27-altered diffuse midline glioma of the brainstem: from molecular mechanisms to targeted interventions. Cells, 13:1122, Jun 2024. URL: https://doi.org/10.3390/cells13131122, doi:10.3390/cells13131122. This article has 14 citations.

27. (NCT07501156 chunk 1): H3K27M-specific Immune Effector Cells Targeting DMG/DIPG. Shenzhen Geno-Immune Medical Institute. 2026. ClinicalTrials.gov Identifier: NCT07501156