{"entity":{"id":"h3-k27m","kind":"biomarker","name":"H3 K27M mutation","aka":["H3 K27M","H3K27M","H3F3A K27M","H3-3A K27M","K27M","H3 K27-altered","H3 K27M-mutant diffuse midline glioma"],"tldr":"H3 K27M is a single change in a histone that defines diffuse midline glioma, including the brain-stem tumour DIPG. In 2025 dordaviprone became the first drug approved for tumours carrying it.","summary":"The K27M substitution in H3-3A (or H3C2/H3C3, the H3.1 genes) is detected by a mutation-specific antibody on immunohistochemistry or by sequencing; WHO CNS5 groups these tumours as diffuse midline glioma, H3 K27-altered, grade 4. Dordaviprone (Modeyso, August 2025, accelerated approval) is labelled for adult and paediatric patients from one year with diffuse midline glioma harbouring an H3 K27M mutation and progressive disease after prior therapy. Radiotherapy remains the first treatment; the ACTION trial (NCT05580562) tests dordaviprone after radiotherapy.","asOf":"2026-09-23","links":[{"label":"MODEYSO prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad45b43e-fdef-47ad-9c34-055b41bdc576"}],"tags":["biomarker","glioma","paediatric"],"related":["mgmt-promoter-methylation","idh1-r132"],"cancers":["dipg-dmg","paediatric-high-grade-glioma"],"sections":[],"technologies":[],"targets":[],"drugs":["dordaviprone"],"companies":[],"institutions":[],"pathways":[],"terms":["h3k27m"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"h3-3a","measurement":"sequencing-variant","scoringRule":{"text":"The H3 K27M substitution by immunohistochemistry with a mutation-specific antibody (with loss of H3K27me3 staining) or by sequencing of H3-3A, H3C2 or H3C3.","quote":"MODEYSO is indicated for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad45b43e-fdef-47ad-9c34-055b41bdc576","sourceLabel":"MODEYSO prescribing information"},"thresholds":[{"value":"H3 K27M mutation, progressive disease after prior therapy","drugId":"dordaviprone","cancerId":"dipg-dmg","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad45b43e-fdef-47ad-9c34-055b41bdc576","quote":"MODEYSO is indicated for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.","status":"current"}],"tests":["caris-mi-profile","foundationone-cdx","tempus-xt"],"assays":[],"companionDiagnostics":[],"forPatient":"An H3 K27M result confirms a diffuse midline glioma. Radiotherapy is still the first treatment, and if the tumour grows afterwards dordaviprone capsules are now on label for adults and children over one year. Trials of dordaviprone given straight after radiotherapy are recruiting."},"route":"/biomarkers/h3-k27m/","neighbours":{"biomarker":[{"id":"idh1-r132","kind":"biomarker","name":"IDH1 R132 mutation","route":"/biomarkers/idh1-r132/"},{"id":"mgmt-promoter-methylation","kind":"biomarker","name":"MGMT promoter methylation","route":"/biomarkers/mgmt-promoter-methylation/"}],"cancer":[{"id":"dipg-dmg","kind":"cancer","name":"Diffuse midline glioma, H3 K27-altered (including DIPG)","route":"/cancers/dipg-dmg/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"}],"drug":[{"id":"dordaviprone","kind":"drug","name":"Dordaviprone","route":"/drugs/dordaviprone/"}],"term":[{"id":"h3k27m","kind":"term","name":"H3 K27M (diffuse midline glioma)","route":"/terms/h3k27m/"}],"target":[{"id":"h3-3a","kind":"target","name":"Histone H3.3 (H3-3A)","route":"/targets/h3-3a/"}]}}