A genome-wide screen identifies E2F6 as critical factor for TMZ chemoresistance in EGFRvIII expressing GBM (CRISPR library RNA-seq)

We conducted a genome-wide screen by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 library to identify genes which are particularly resistant to EGFRvIII GBM cells under the chemo-stress of TMZ. In vitro and in vivo validation of EGFRvIII-specific targets revealed several strong hits, including E2F6. Mechanistic studies demonstrated that E2F6 reveals its resistance to TMZ through NF-?B and TMZ inducement.EGFRvIII GBM cells under the chemo-stress of TMZ. Overall design: Examination of TMZ resistant and sensitive genes in U87EGFRvIII cells, each with 3 replicates.