WITHDRAWAL: Significant effect of anti-tyrosine kinase inhibitor (Gefitinib) on overall survival of the Glioblastoma (GBM) patients in the backdrop of mutational status of EGFR and PTEN genes.
Here, through integrated epigenome and transcriptome analyses of cell lines, genotyped clinical samples, and TCGA data, we show that EGFR mutations remodel the activated enhancer landscape of GBM, promoting tumorigenesis through a SOX9 and FOXG1-dependent transcriptional regulatory network in vitro and in vivo.
Here we demonstrate that a subpopulation of endothelial cells within glioblastomas harbour the same somatic mutations identified within tumour cells, such as amplification of EGFR and chromosome 7.
Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM), generated by deletion of exons 2 to 7 of EGFR.
More than one-half (62.5%) of the glioblastomas with amplified EGFR genes also showed coamplification of rearranged EGFR genes and concomitant expression of aberrant mRNA species.
Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies.
These receptors are de-regulated in many human tumors, and EGFR amplification, overexpression, and mutations are detected at a high frequency in carcinomas and glioblastomas, which are tumors of epithelial and glial origin, respectively.
Delta epidermal growth factor receptor (ΔEGFR), an in-frame deletion mutant of the extracellular ligand-binding domain, which occurs in about 30% of glioblastoma, is a potent oncogene that promotes tumor growth and progression.
Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas.
The findings of this study indicate a highly invasive phenotype associated with the EGFR<sup>A289V</sup> mutation in glioblastoma, postulating EGFR<sup>A289V</sup> as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
Amplification/overexpression of the epidermal growth factor receptor (EGFR) gene as a signature genetic abnormality of GBM tumors can be a chemoresistance mechanism.
The presented work shows that sequential EGFR amplification and EGFRvIII mutations might represent concerted evolutionary events that drive the aggressive nature of GBM by promoting invasion and angiogenesis via distinct signaling pathways.
None of the primary low-grade and none of the recurrent high-grade tumors (7 anaplastic astrocytomas, 10 anaplastic oligodendrogliomas, 4 anaplastic oligoastrocytomas, and 5 glioblastomas) showed evidence of EGFR gene amplification.
In 2 of the glioblastomas with EGFR gene amplification, a rearrangement of the gene affecting the extracellular domain of the receptor was identified and DNA sequence analyses revealed an identical deletion-rearrangement of 801 base pairs between exons 2 to 7, resulting in an in-frame fusion of exons 1 and 8.
Activation of signaling by the epidermal growth factor receptor (EGFR) through gene amplification or rearrangement is common in human malignancy, especially in a large fraction of de novo glioblastomas multiforme (GBMs).
We aimed to explore the prognostic impact of epidermal growth factor receptor copy number gain (EGFR CN gain), one of the most common genetic alterations in IDH-WT glioma, in young adults with IDH-WT GBM.