Pluto Bioinformatics

GSE84462: Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven Group 3 medulloblastoma [RNA-Seq]

Bulk RNA sequencing

The most aggressive of four medulloblastoma (MB) subgroups are cMYC-driven Group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 trimethylase of polycomb repressive complex-2. Yet, engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression. Candidate oncogenic drivers upregulated following Ezh2 deletion included Gfi1, a proto-oncogene frequently activated in human G3 MBs. Gfi1 disruption antagonized the tumor promoting effects of Ezh2 loss; conversely, Gfi1 overexpression collaborated with Myc to bypass effects of Trp53 inactivation in primary cerebellar neuronal progenitors thereby driving MB progression. Although negative epigenetic regulation of Gfi1 by Ezh2 may restrain MB development, Gfi1 activation can bypass these effects. SOURCE: David Finkelstein (david.finkelstein@stjude.org) - St Jude Children's Research Hospital