Polycomb repressive complex 2 in the driver's seat of childhood and young adult brain tumours

Deregulation of the epigenome underlies oncogenesis in numerous primary brain tumours in children and young adults. In this review, we describe how recurrent mutations in isocitrate dehydrogenases or histone 3 variants (oncohistones) in gliomas, expression of the oncohistone mimic enhancer of Zeste homologs inhibiting protein (EZHIP) in a subgroup of ependymoma, and epigenetic alterations in other embryonal tumours promote oncogenicity. We review the proposed mechanisms of cellular transformation, current tumorigenesis models and their link to development. We further stress the narrow developmental windows permissive to their oncogenic potential and how this may stem from converging effects deregulating polycomb repressive complex (PRC)2 function and targets. As altered chromatin states may be reversible, improved understanding of aberrant cancer epigenomes could orient the design of effective therapies.

Automated summary

This review discusses the deregulation of the epigenome in primary brain tumors in children and young adults, highlighting recurrent mutations, protein expression, and epigenetic alterations that promote oncogenicity. The review also emphasizes the narrow developmental windows permitting oncogenic potential and the potential reversibility of altered chromatin states.