MGMT deletion

We integrate targeted epigenome editing with unbiased genome-wide approaches to build a novel discovery and therapeutic platform in glioblastoma, a framework that is well suited for targeting diseases with known or suspected epigenetic vulnerabilities.

Here we performed epigenome editing using CRISPRoff to stably silence MGMT through induced promoter methylation, as a therapeutically tractable approach for potentiating GBM to temozolomide (TMZ) or lomustine (CCNU). We integrate targeted epigenome editing with unbiased genome-wide approaches to build a novel discovery and therapeutic platform in glioblastoma, a framework that is well suited for targeting diseases with known or suspected epigenetic vulnerabilities.

This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.

This study confirmed the role of extent of resection (EOR) at first and at recurrence as a significant predictor of outcome in patients with recurrent GBM. In addition, this study highlighted the concept of a dynamic evolution of GBM genome after initial surgical resection, supporting the need of further studies to investigate the clinical and therapeutic implications of the changes in genetic profiles after initial surgery.