Discussion
Functional roles
EGFR plays an essential role in the nervous system in various ways, including 1) Maintenance of the neural stem cells pool, 2) Maturation and functions of astrocytes, 3) Oligodendrogenesis, and 4) neurite outgrowth in the CNS. They also play a role in PNS development\cite{Romano2020}. As a result, alterations in EGFR, like GBM, possibly have their causes rooted in the appropriate mutations. In lung cancers, the ramifications of mutations in kinase domains get expressed differently to their interactions and cross-talk with other signaling components in the milieu. For example, there is a substantial cross-talk and interplay between other tyrosine kinase mediators like Vascular Endothelial Growth Factor (VEGF) and Interferon-Gamma(IFNg)\cite{Attili2018}\cite{Passaro2020}.
Compared to the EGFR gene, the EGFRvIII variant has missing L1 and CR1 domains due to the deletion of exons 2-7 (Fig 2). This truncation results in the inability of the receptor to bind to any ligand, thus becoming an important driver in tumor progression and a marker of poor prognosis\cite{Gan2013}. There are two variations of EGFR vIV, namely EGFR-vIVa and EGFR-vIVb, which contain deletions of exons 25-27 and 25-26, respectively \cite{Pines2010}. Thus, EGFRvIII and EGFRvIVa/b are both mutants of the epidermal growth factor receptor (EGFR), but they differ in the parts of the receptor that they lack. EGFRvIII lacks a portion of the ligand-binding cleft, while EGFRvIVa/b lacks internal segments distal to the intracellular tyrosine kinase domain.