ArticleOncogene2013
EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 138 citations in OpenAlex.
- A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study.Neuro-oncology · 2015Trial
- Trial
- Co-expression of non-signaling CARs enhances EGFRvIII-specific CAR T-cell cytotoxicity against head and neck squamous cell carcinoma.BMC cancer · 2026Article
- EGFRvIII Reduces Neural Stem/Progenitor Marker Expression in GFAP-Negative iNSCs: Evidence for a Context-Dependent Cellular Response.International journal of molecular sciences · 2026Article
- Theranostic vNAR-Based Immunoconjugates Achieve Selective Intracellular Cisplatin Delivery in Embedded 3D HER2-Positive Breast Cancer In Vitro Model.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Heat up and Destroy: Immunotherapy of "Cold" Tumors Using the Example of Glioblastoma.International journal of molecular sciences · 2026Review
- Immunotherapy and targeted therapy for high grade gliomas: current and future directions.Journal of neuro-oncology · 2025Review
- A brain cancer microtissue model for studying tumor cell and neural cell interactions.Scientific reports · 2025Article
- Extrachromosomal DNA-Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma.Cancer discovery · 2025Article
- Comparative efficacy and safety of therapeutic strategies for EGFRvIII positive recurrent glioblastoma.iScience · 2025Article
- Intratumoral heterogeneity and drug resistance in cancer.Cancer cell international · 2025Review
- The radiogenomic and spatiogenomic landscapes of glioblastoma and their relationship to oncogenic drivers.Communications medicine · 2025Article
- Isolation and Characterization of the First Antigen-Specific EGFRvIII vNAR from Freshwater Stingray (International journal of molecular sciences · 2025Article
- Unraveling the immunosuppressive microenvironment of glioblastoma and advancements in treatment.Frontiers in immunology · 2025Review
- New approaches to overcome radioresistance in glioblastoma: mechanisms, targets and role of innovative therapies, new particles and non-photon radiotherapy in 2024. A systematic review.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2025Review
- Advances in CAR-T therapy for central nervous system tumors.Biomarker research · 2024Review
- Identifying cell lines across pan-cancer to be used in preclinical research as a proxy for patient tumor samples.Communications biology · 2024Article
- Article
- vNARs as Neutralizing Intracellular Therapeutic Agents: Glioblastoma as a Target.Antibodies (Basel, Switzerland) · 2024Review
- Intratumoral thrombosis as a histological biomarker for predicting epidermal growth factor receptor alteration and poor prognosis in patients with glioblastomas.Journal of neuro-oncology · 2023Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Amplification and rearrangements of the epidermal growth factor receptor (EGFR) gene are frequently found in glioblastoma multiforme (GBM). The most common variant is EGFR variant III (EGFRvIII). Research suggests that EGFRvIII could be a marker for a cancer stem cell or tumor-initiating population. If amplification and rearrangement are early events in tumorigenesis, this implies that they should be preserved throughout the tumor. However, in primary GBM, EGFRvIII expression is focal and sporadic. Unexpectedly, we found EGFR amplification and rearrangement throughout the tumor, including regions with no EGFRvIII expression, suggesting that mechanisms exist to modulate EGFRvIII expression even in the presence of high gene amplification. To study this phenomenon, we characterized three GBM cell lines with endogenous EGFRvIII. EGFRvIII expression was heterogeneous, with both positive and negative populations maintaining the genetic alterations, akin to primary tumors. Furthermore, EGFRvIII defined a hierarchy where EGFRvIII-positive cells gave rise to additional positive and negative cells. Only cells that had recently lost EGFRvIII expression could re-express EGFRvIII, providing an important buffer for maintaining EGFRvIII-positive cell numbers. Epigenetic mechanisms had a role in maintaining heterogeneous EGFRvIII expression. Demethylation induced a 20-60% increase in the percentage of EGFRvIII-positive cells, indicating that some cells could re-express EGFRvIII. Surprisingly, inhibition of histone deacetylation resulted in a 50-80% reduction in EGFRvIII expression. Collectively, this data demonstrates that EGFR amplification and rearrangement are early events in tumorigenesis and EGFRvIII follows a model of hierarchical expression. Furthermore, EGFRvIII expression is restricted by epigenetic mechanisms, suggesting that drugs that modulate the epigenome might be used successfully in glioblastoma tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.