Validity of Targeted Next-Generation Sequencing in Routine Care for Identifying Clinically Relevant Molecular Profiles in Non–Small-Cell Lung Cancer: Results of a 2-Year Experience on 1343 Samples

Publication date: July 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 4Author(s): Antoine Legras, Marc Barritault, Anne Tallet, Elizabeth Fabre, Alice Guyard, Bastien Rance, William Digan, Nicolas Pecuchet, Etienne Giroux-Leprieur, Catherine Julie, Stéphane Jouveshomme, Véronique Duchatelle, Véronique Giraudet, Laure Gibault, Alain Cazier, Jean Pastre, Françoise Le Pimpec-Barthes, Pierre Laurent-Puig, Hélène BlonsTheranostic assays are based on single-gene testing, but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single-gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations, and NGS mutation profiles were analyzed on a large series of non–small-cell lung cancers (n = 1343). The R2 correlation between expected and measured allelic ratio, using commercial samples, was>0.96. Mutation detection threshold was 2% for 10 ng of DNA input. κ Scores for TaqMan versus NGS were 0.99 (95% CI, 0.97–1.00) for EGFR and 0.98 (95% CI, 0.97–1.00) for KRAS after exclusion of rare EGFR (n = 40) and KRAS (n = 60) mutations. NGS identified 693 and 292 mutations in validated and potential oncogenic drivers, respectively. Significant associat...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research