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

  • Laboratory Investigation
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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.

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Acknowledgments

We would like to thank Dr. Mario Medvedovic and Dr. Jing Chen from the Department of Environmental Health at the University of Cincinnati for their help with the whole genome sequencing data analysis. We would also like to thank Ruth Steele and Susanne Sifri from Neuro-oncology clinical trials unit for their support and Dr. Ady Kendler for pathology. This work was supported by funds from the University of Cincinnati and from the Neuroscience Foundation/Mayfield Clinic.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, 231, Albert Sabin Way, Cincinnati, OH, 45267-0508, USA

    Mohamad A. Salkeni, Ahmad Zarzour & El Mustapha Bahassi

  2. Department of Neurosurgery, Mayfield Clinic, University of Cincinnati, P.O. Box 670515, Cincinnati, OH, 45267-0515, USA

    Tracy Y. Ansay, Christopher M. McPherson, Ronald E. Warnick & Olivier Rixe

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  1. Mohamad A. Salkeni
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  2. Ahmad Zarzour
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Correspondence to El Mustapha Bahassi.

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Salkeni, M.A., Zarzour, A., Ansay, T.Y. et al. Detection of EGFRvIII mutant DNA in the peripheral blood of brain tumor patients. J Neurooncol 115, 27–35 (2013). https://doi.org/10.1007/s11060-013-1209-0

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  • DOI: https://doi.org/10.1007/s11060-013-1209-0

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