Somatic histone 3 mutations in DIPG

Suzy Baker’s group at St Jude Childrens Research Hospital in Memphis, TN, USA, has just published in Nature Genetics the first findings from the whole genome resequencing of DIPG specimens as part of the St Jude / Washington University Pediatric Cancer Genome Project. They made the startling discovery that fully 78% of DIPG samples harboured mutations at a key residue in two histone H3 variant genes – H3F3A and HIST1H3B.
Along with a concurrent publication in Nature by the groups of Nada Jabado (Montreal) and Stefan Pfister (Heidelberg) of H3F3A mutations in paediatric non-brainstem high grade glioma, we have the most definitive evidence of the biological distinctiveness of these lesions in the paediatric setting. Most intriguing is the different mutational spectrum in these genes between anatomical sites in children – K27 mutations are more common in DIPG than in supratentorial tumours, whilst G34 mutations were entirely absent from brainstem and thalamic lesions. Further investigating such biological differences remains a key goal of the DIPG Repository.

Chris Jones