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• W2898483550 abstract "The analysis of EGFR activating mutations and ALK rearrangement is a routine procedure in qualification of NSCLC patients for molecularly targeted therapy. Targeted sequencing, as a type of NGS, allows more comprehensive analysis of low-frequency variations in suppressors and oncogenes that are commonly mutated in solid tumors. In the following study we analyzed a molecular landscape of NSCLC patients harboring EGFR activating mutations who response for EGFR TKIs. The studied group included 19 Caucasian patients (7 male and 12 female, median age 65±12 years, 4 current smokers, 12 non-smokers and 3 former-smokers) with lung adenocarcinoma. 12 (63%) deletions in exon 19, 4 (21%) substitutions Leu858Arg in exon 21, 2 (11%) insertions A763_Y764 in exon 20 and 1 (5%) substitution Thr790Met in exon 20 of EGFR gene were detected using real-time PCR technique. Four non-smoking patients (median age 65±12 years) with lung adenocarcinoma and wild-type (wt) of EGFR gene were a control group. The DNA for the analysis was isolated from FFPE tissue or cellblocks and the mutational landscape was evaluated using Illumina’s TruSight Tumor 26 panel on miSeq platform (Illumina, USA). The targeted sequencing confirmed lack of EGFR gene mutations in control group and the presence of EGFR mutations in 84% (16/19) of patients with these mutations confirmed in routine diagnostics - all deletions in exon 19 and substitutions in exon 21 were confirmed. Targeted sequencing did not identify rare mutations in exon 20. NGS compared to real-time PCR technique achieved 86,95% accuracy with 84,21% of sensitivity and 100% of specificity or PPV and NPV values reached 100% and 57,10%, respectively. The targeted sequencing allowed to identify 166 variants in 25 out of 26 genes covered by the analysis. The most frequently mutated suppresors were TP53, MSH6 and APC (38%; 19% and 17% respectively) and oncogenes were MET, PDGFR and EGFR-AS1 (31%, 14% and 13% respectively). The frequency of particular variants was significantly higher in smokers than in non-smokers (p=0,0002; χ2=16,94). U-Man Whitney test showed that the median number of genetic alternations in EGFR mutated group was significantly higher than in wt EGFR group (p=0.0091; median: 17 vs 11 respectively). The targeted sequencing allowed to detect the most common activating mutations in EGFR gene and numerous variants both in suppressors and oncogenes. NGS showed too low sensitivity for detection of rare EGFR mutations. The molecular landscape was more unpredictable and varied in smokers compare to non-smokers." @default.
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• W2898483550 date "2018-10-01" @default.
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• W2898483550 title "P1.13-14 The Molecular Landscape of Lung Adenocarcinomas with Activating EGFR Gene Mutations Determined by Targeted-Sequencing" @default.
• W2898483550 doi "https://doi.org/10.1016/j.jtho.2018.08.871" @default.
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