Frequently asked questions (FAQs) about DMG
Find important information about diffuse midline glioma (DMG) for you and your patients
FAQs
Answers to questions about H3 K27M–mutant DMG.
The H3 K27M mutation results in an alteration of histone H3 function, disrupting normal gene regulation and contributing to activation of oncogenic pathways. Gliomas harboring this mutation are typically aggressive and associated with poor prognoses.1,2
There are an estimated 2000 cases of H3 K27M–mutant glioma in the United States every year.3,*
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers recommend screening for mutations in H3 K27M in patients with imaging suggestive of high-grade glioma.4,5
When a patient presents with imaging suggestive of high-grade glioma, the NCCN recommends biopsy, including when surgical resection is not possible. A guiding principle of biopsy is to acquire enough tissue for histological and molecular profiling, and that should be the goal in these cases.4,5
Immunohistochemistry and next-generation sequencing are among the tests that can be used to detect the H3 K27M mutation and should be added to routine testing. Methylation profiling may be considered in addition to these tests to provide more insights.4-9
Imaging alone cannot identify the H3 K27M mutation. Accurate diagnosis requires tissue acquisition and molecular profiling to confirm the presence or absence of a mutation.6,10,11
The World Health Organization (WHO) classifies diffuse gliomas with an H3 K27M mutation as WHO CNS Grade 4 (aggressive, spreads rapidly) irrespective of diffuse glioma histology.1,2
Identifying the H3 K27M mutation can inform clinical decision-making and open up treatment options. Because of this, the NCCN recommends routine screening for H3 K27M mutations in patients with high-grade glioma.4,5
Yes. MODEYSO (dordaviprone) is the first and only FDA-approved treatment for H3 K27M–mutant DMG with progressive disease following prior therapy in patients 1 year of age and older.12
Accelerated approval for adult and pediatric (≥1 year of age) patients based on overall response rate and duration of response. Continued approval may be contingent upon confirmatory trials.12
H3, histone 3; K, lysine; M, methionine.
*Inclusive of midline and nonmidline glioma.
References: 1. Saratsis AM, Knowles T, Petrovic A, Nazarian J. H3K27M mutant glioma: disease definition and biological underpinnings. Neuro Oncol. 2024;26(suppl 2):S92-S100. 2. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251. 3. Data on file. Jazz Pharmaceuticals, Inc. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Central Nervous System Cancers V.1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 24, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.3.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed August 28, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Vallero SG, Bertero L, Morana G, et al. Pediatric diffuse midline glioma H3K27-altered: a complex clinical and biological landscape behind a neatly defined tumor type. Front Oncol. 2023;12:1082062. 7. Bechet D, Gielen GG, Korshunov A, et al. Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas. Acta Neuropathol. 2014;128(5):733-741. 8. Kim T, Lee A, Ahn S, Park JS, Jeun SS, Lee YS. Comprehensive molecular genetic analysis in glioma patients by next generation sequencing. Brain Tumor Res Treat. 2024;12(1):23-39. 9. Penkova A, Kuziakova O, Gulaia V, et al. Comprehensive clinical assays for molecular diagnostics of gliomas: the current state and future prospects. Front Mol Biosci. 2023;10:1216102. 10. Horbinski C, Solomon DA, Lukas RV, et al. Molecular testing for the World Health Organization classification of central nervous system tumors: a review. JAMA Oncol. 2025;11(3):317-328. 11. Gajjar A, Mahajan A, Bale T, et al. Pediatric central nervous system cancers, version 2.2025. J Natl Compr Canc Netw. 2025;23(3):113-130. 12. MODEYSO™. Package insert. Jazz Pharmaceuticals, Inc; 2026.
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