title: 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.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, 231, Albert Sabin Way, Cincinnati, OH, 45267-0508, USA.
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Salkeni
authors.forename: Ahmad
authors.initials: A
authors.lastname: Zarzour
authors.forename: Tracy Y
authors.initials: TY
authors.lastname: Ansay
authors.forename: Christopher M
authors.initials: CM
authors.lastname: McPherson
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Warnick
authors.forename: Olivier
authors.initials: O
authors.lastname: Rixe
authors.forename: El Mustapha
authors.initials: el M
authors.lastname: Bahassi
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood*; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics*; D005240:Feasibility Studies; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors