H3 K27M mutation

aka H3 K27M, H3K27M, H3F3A K27M, H3-3A K27M, K27M, H3 K27-altered, H3 K27M-mutant diffuse midline glioma

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.

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.

Part ofHistone H3.3 (H3-3A)· H3-3A All readouts

Histone H3.3 (H3-3A): what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · H3.3 is one of the histone proteins DNA wraps around; a single change at position 27 (K27M) locks brain-stem and midline gliomas in an immature state and defines the diagnosis.

Sequencing 1 approval threshold

What it means for a patient

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.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

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.

“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.”
MODEYSO prescribing information

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
H3 K27M mutation, progressive disease after prior therapy	Dordaviprone	Diffuse midline glioma, H3 K27-altered (including DIPG)	FDA	label

Drugs whose label names it

Dordaviprone

Tests that measure it

Tempus xT and xT CDx FoundationOne CDx Caris MI Profile

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.