Gene of the month: H3F3A and H3F3B.

and genes are located at 1q42.12 and 17q25.1, respectively, and encode identical H3.3 core histone proteins which form part of the histone hetero-octamer complex. Histones function by packaging DNA into small units, the nucleosome, and are highly susceptible to epigenetic post-translational modification. H3 K27 mutations have been shown to inhibit the polycomb repressive complex 2, which is normally involved in epigenetic gene silencing. Mutations in and are increasingly recognised in a variety of solid tumours. Point mutations in have been described in giant cell tumour of bone and paediatric-type diffuse high-grade gliomas. Mutations in have been described in chondroblastoma. Loss of trimethylation of H3 K27 is characteristic of most sporadic and radiation-associated malignant peripheral nerve sheath tumours. Immunohistochemistry with a variety of novel antibodies directed against specific mutations, as well as loss of H3K27me3 staining, may be useful in specific settings and in diagnostically challenging cases.