MET Exon 14 Alterations and New Resistance Mutations to Tyrosine Kinase Inhibitors: Risk of Inadequate Detection with Current Amplicon-Based NGS Panels

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MET Exon 14 Alterations and New Resistance Mutations to Tyrosine Kinase Inhibitors: Risk of Inadequate Detection with Current Amplicon-Based NGS Panels Brigitte Poirot, PharmD, Ludovic Doucet, MD, Shirine Benhenda, PhD, Jérôme Champ, MS, Véronique Meignin, MD, PhD, Jacqueline Lehmann-Che, PharmD, PhD Journal of Thoracic Oncology Volume 12, Issue 10, Pages 1582-1587 (October 2017) DOI: 10.1016/j.jtho.2017.07.026 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Schematic diagram showing position of indels (red dashes) and substitutions (red arrowheads) in splice site junctions or codon Tyr1003 of mesenchymal epithelial transition factor gene exon 14 (METex14) identified in our cohort and target regions of the two panels used in our laboratory. Journal of Thoracic Oncology 2017 12, 1582-1587DOI: (10.1016/j.jtho.2017.07.026) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 False-negative case with amplicon-based next-generation sequencing technology. (A) Juxtaposed view of undetected deletion and primer positions (panel TS26). The deletion was not detected because of its location inside the primer binding site of the two adjacent amplicons covering mesenchymal epithelial transition factor gene exon 14. (B) Reads visualization. For the first amplicon, primer hybridization was possible only on wild-type DNA (1); amplification of mutated DNA failed, a phenomenon call allele drop-out. For the second amplicon, primer hybridization was possible because only the last nucleotides of the primer were located under the deletion. Wild-type (2) and mutated (3) DNA were amplified, but because of data processing and notably primer trimming, the deletion was removed (3) and its presence can only be suspected owing to the low depth of sequencing (4). Journal of Thoracic Oncology 2017 12, 1582-1587DOI: (10.1016/j.jtho.2017.07.026) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions