The H3.3K27M oncohistone affects replication stress outcome and provokes genomic instability in pediatric glioma

12 November 2021

A study by Bočkaj, Martini, and de Camargo Magalhães et al.

Out now in PLoS Genetics –

The discovery that mutations in histone H3 variants frequently occur in malignant pediatric glioma created great interest into the mechanism of transformation of these so-called oncohistones. Yet whereas most studies are directed at understanding the role of mutant H3 in deregulating gene expression, the Bruggeman lab studied if and how it contributes to genomic instability – a relatively unexplored research avenue. It was found that the H3.3K27M oncohistone increases sensitivity to replication stress during S-phase, ultimately leading to mitotic aberrancies. This finding can explain why childhood high-grade glioma is among the most genomically unstable cancers.

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