Histone H3 (K27M Mutant Specific) (D3B5T) Rabbit mAb recognizes endogenous levels of K27M mutant histone H3.1, H3.2, and H3.3 proteins. The antibody may cross-react with wild-type histone H3.1, 3.2, and 3.3 when used at a high concentration. Careful titration of this antibody may be required to obtain optimal specificity.

Rat, Xenopus, Pig

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to K27M mutant sequence of human histone H3.3 protein.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brainstem astrocyte tumor arising mostly in children, leading to a long-term survival rate of less than 10%. Multiple whole-genome sequencing studies of DIPG patients identified commonly occurring mutations in the H3F3A gene encoding histone H3.3. One of these mutations, a lysine to methionine amino acid substitution (K27M), is found in up to 78% of DIPGs and 22% of non-brainstem pediatric gliomas (1-3). This mutation is associated with poor prognosis, with a mean survival time of 0.73 years for patients with the K27M mutation versus 4.6 years for patients without the mutation (1-3). Expression of the K27M mutant histone H3 is accompanied by a dramatic reduction in the levels of polycomb repressive complex 2 (PRC2)-mediated trimethylation of histone H3, changes in the distribution of PRC2 on the genome, and altered expression of genes associated with various cancer pathways (4-6).