Molecular Diagnosis & Therapy

, Volume 21, Issue 4, pp 431–436 | Cite as

Identification of a Novel Somatic Mutation Leading to Allele Dropout for EGFR L858R Genotyping in Non-Small Cell Lung Cancer

  • Helio A. Costa
  • Joel W. Neal
  • Carlos D. Bustamante
  • James L. ZehnderEmail author
short communication



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.


Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Mutation Epidermal Growth Factor Receptor Gene L858R Mutation Epidermal Growth Factor Receptor Mutation Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards

Conflict of interest

H. A. C. and J. L. Z. have no conflicts of interest to report, J.W.N. is a consultant for Clovis Oncology, CARET, Nektar, Boehringer Ingelheim, ARMO BioScience and ARIAD. C.D.B. is on the scientific advisory boards (SAB) of AncestryDNA, BigDataBio, Etalon DX, Liberty Biosecurity, and Personalis. He is also a founder and SAB chair of IdentifyGenomics. None of these entities played a role in the design, execution, interpretation, or presentation of this study.


This research was supported by grants from the National Institutes of Health (ClinGen 4U01HG007436-04 to C.D.B.; NCI 2PO1CA49605 to J.L.Z.).


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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Helio A. Costa
    • 1
  • Joel W. Neal
    • 2
  • Carlos D. Bustamante
    • 1
    • 3
  • James L. Zehnder
    • 4
    Email author
  1. 1.Department of GeneticsStanford University School of MedicineStanfordUSA
  2. 2.Division of Oncology, Department of MedicineStanford University School of MedicineStanfordUSA
  3. 3.Department of Biomedical Data ScienceStanford University School of MedicineStanfordUSA
  4. 4.Department of PathologyStanford University School of MedicineStanfordUSA

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