Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas

Abstract

To identify somatic mutations in pediatric diffuse intrinsic pontine glioma (DIPG), we performed whole-genome sequencing of DNA from seven DIPGs and matched germline tissue and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem pediatric glioblastomas (non-BS-PGs). We found that 78% of DIPGs and 22% of non-BS-PGs contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, that caused a p.Lys27Met amino acid substitution in each protein. An additional 14% of non-BS-PGs had somatic mutations in H3F3A causing a p.Gly34Arg alteration.

Figure 1. Recurrent somatic mutations in H3F3A and HIST1H3B

Sanger sequencing chromatograms showing representative H3F3A or HIST1H3B mutations encoding p.K27M substitutions, or H3F3A mutation encoding p.G34R substitution in the indicated tumour compared to matched normal DNA. Arrow indicates mutation. SJHGG001 and SJHGG079 are DIPGs, SJHGG043 is a non-brainstem paediatric glioblastoma.