title: Identification of a Novel Somatic Mutation Leading to Allele Dropout for EGFR L858R Genotyping in Non-Small Cell Lung Cancer.
abstract: While PCR-based genotyping methods abound in molecular testing for lung cancer therapy, these approaches may not provide the robust sensitivity to detect accurate genotypes in a variable cancer genomic background.
  
  
  
  Here, we describe a study of a clinical tumor specimen containing a novel somatic single nucleotide variant that caused allele drop-out in EGFR L858R genotyping, resulting in a false-negative interpretation and impacting patient clinical management.
  
  
  
  We demonstrate that a subsequent unbiased next-generation sequencing approach correctly identified the driver mutation, and therefore may be more reliable for somatic variant detection.
  
  
  
  These findings magnify the potential pitfalls of PCR amplification-based approaches and stress the importance of unbiased and sensitive molecular testing strategies for therapeutic marker detection as molecular testing becomes the standard for determining clinical management of cancer patients.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Helio A
authors.initials: HA
authors.lastname: Costa
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Neal
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Bustamante
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA. zehnder@stanford.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Zehnder
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005188:False Negative Reactions; D015870:Gene Expression; D005838:Genotype; D060005:Genotyping Techniques; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors