Identification of a Novel Somatic Mutation Leading to Allele Dropout for EGFR L858R Genotyping in Non-Small Cell Lung Cancer. Molecular diagnosis & therapy Costa, H. A., Neal, J. W., Bustamante, C. D., Zehnder, J. L. 2017


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.

View details for DOI 10.1007/s40291-017-0275-y

View details for PubMedID 28357677