Detection of EGFRvIII mutant DNA in the peripheral blood of brain tumor patients

Abstract

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and remains incurable despite multimodal intensive treatment regimens including surgical resection, radiation and chemotherapy. EGFRvIII is a truncated extracellular mutant of the EGF receptor (EGFR) found in about a third of GBMs. It confers enhanced tumorigenic behavior and is associated with chemo- and radio-resistance. GBM patients testing positive for EGFRvIII have a bleaker prognosis than those who do not. Targeting EGFRvIII positive tumors via vaccines or antibody-drug-conjugates represents a new challenging therapeutic avenue with potential great clinical benefits. In this study, we developed a strategy to detect EGFRvIII deletion in the circulating tumor DNA. The overall goal is to identify a simple and robust biomarker in the peripheral blood of patients diagnosed with GBM in order to follow their disease status while on treatment. Thirteen patients were included in this study, three of which were found to carry the EGFRvIII deletion. The circulating DNA status for EGFRvIII correlates with the analysis performed on the respective tumor samples, and its level seems to correlate with the extent of the tumor resection. This semi-quantitative blood biomarker may represent a strategy to (1) screen patients for an anti-EGFRvIII therapy and (2) monitor the patients' response to treatment.

A practical review of prognostic correlations of molecular biomarkers in glioblastoma

“…EGFRvIII can be detected in the peripheral blood of brain tumor patients, opening the possibility of screening patients for anti-EGFRvIII therapies and monitoring response. 41 Several studies suggest the potential of EGFR as a prognostic factor in GBM given the presence of a specific EGFRvIII mutational variant with a clear role in gliomagenesis, 29 while others have not shown a clinical correlation between EGFR and survival. 16 In one study, EGFR amplification resulted in significantly lower OS than did EGFR wild type (13.3 vs 26.6 months); 29 however, a study of long-term survivors of GBM (> 36 months) showed that alterations in EGFR were not significant predictors.…”

Soluble Urokinase Receptor Is Released Selectively by Glioblastoma Cells That Express Epidermal Growth Factor Receptor Variant III and Promotes Tumor Cell Migration and Invasion*

“…To test whether suPAR is increased in plasma from patients with EGFRvIII-positive GBMs, we obtained plasma samples and applied a PCR assay to detect circulating DNA derived from full-length WT-EGFR and EGFRvIII (47). We used previously described primers (41), which flank the deletion region in EGFRvIII, to specifically detect DNA from this EGFR variant.…”

Critical Molecular and Genetic Markers in Primary Brain Tumors with Their Clinical Importance

“…About 10-60% of the patients with GBM have EGFRvIII which can be detected in the peripheral blood of brain tumors. The detection of this mutation in brain cancer patients has great importance for anti-EGFRvIII therapies and patients can be monitored to track their response to these therapies [11,12]. Better and deeper knowledge of mechanistic insights that cause EGFR heterogeneity in GBM will prove to be helpful in identification of drugs with maximum efficacy.…”