Glioblastoma: Histone mutations take the MYCN

摘要

Last month we covered a paper on histone 3 (H3) mutations in paediatric glioblastoma (GBM) that showed that K27M mutations in H3.3 and H3.1 resulted in an inhibition of the Polycomb repressive complex 2 (PRC2) and a change in global histone methylation levels at H3K27. G34R or G34V H3 mutations are also found in cases of GBM in children and young adults, but these do not result in inhibition of PRC2. Instead, Chris Jones and colleagues have found that mutations that affect G34 result in the altered binding of proteins that recognize trimethylated H3K36 (H3K36me3). This results in a gene expression signature that is more commonly seen in the developing forebrain and that is associated with increased MYCN transcription.