Despite advances in our understanding of the molecular underpinnings of glial tumors, most treatments are still largely ineffective. Among these tumors, glioblastomas have proven to be particularly difficult to treat, in large part because of their heterogeneous composition of differentiated and undifferentiated cells and subpopulations of self-renewing brain tumor stem cells (BTSCs). In recent years, the role of oncogenic signaling by the epidermal growth factor receptor (EGFR) during gliomagenesis has been intensely studied. In particular, the EGFRvIII mutation has emerged as the central driver of the classic subtype of glioblastomas.1 Although it is known that EGFRvIII signaling activates protumorigenic signal transducer and activator of transcription 3 (STAT3) signaling, the mechanism by which STAT3 drives tumorigenesis is poorly understood. Jahani-Asl et al2 set out to determine the mechanism by which EGFRvIII and STAT3 induce glioblastomas.
To determine unique gene expression characteristic of EGFRvIII mutant glioblastoma, they performed RNA sequencing of 3 EGFRvIII-expressing glioma cell lines and compared them with a nonmutant control. Two hundred seventy-two candidate targets were identified. They then analyzed EGFRvIII-expressing astrocytes that expressed Stat3 and compared these cells with astrocytes conditionally deleted for Stat3 to determine which EGFRvIII-inducible genes were dependent on Stat3.
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