title: A wide spectrum of EGFR mutations in glioblastoma is detected by a single clinical oncology targeted next-generation sequencing panel.
abstract: With the advent of large-scale genomic analysis, the genetic landscape of glioblastoma (GBM) has become more clear, including characteristic genetic alterations in EGFR. In routine clinical practice, genetic alterations in GBMs are identified using several disparate techniques that consume already limited amounts of tissue and add to overall testing costs. In this study, we sought to determine if the full spectrum of EGFR mutations in GBMs could be detected using a single next generation sequencing (NGS) based oncology assay in 34 consecutive cases. Using a battery of informatics tools to identify single nucleotide variants, insertions and deletions, and amplification (including variants EGFRvIII and EGFRvV), twenty-one of the 34 (62%) individuals had at least one alteration in EGFR by sequencing, consistent with published datasets. Mutations detected include several single nucleotide variants, amplification (confirmed by fluorescence in situ hybridization), and the variants EGFRvIII and EGFRvV (confirmed by multiplex ligation-dependent probe amplification). Here we show that a single NGS assay can identify the full spectrum of relevant EGFR mutations. Overall, sequencing based diagnostics have the potential to maximize the amount of genetic information obtained from GBMs and simultaneously reduce the total time, required specimen material, and costs associated with current multimodality studies.
authors.affiliation: Department of Pathology and Immunology, Division of Neuropathology, Washington University School of Medicine, Saint Louis, MO, United States.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cimino
authors.affiliation: Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, Saint Louis, MO, United States.
authors.forename: Andy
authors.initials: A
authors.lastname: Bredemeyer
authors.affiliation: Division of Statistical Genomics, Washington University School of Medicine, Saint Louis, MO, United States.
authors.forename: Haley J
authors.initials: HJ
authors.lastname: Abel
authors.affiliation: Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, Saint Louis, MO, United States. Electronic address: EDuncavage@path.wustl.edu.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duncavage
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; EGFRvIII; Glioblastoma; Glioma; Next-generation sequencing