Molecular profiling by NGS upon progression disease in advanced stage NSCLC patients

• Published in: Journal of clinical oncology Vol. 39; no. 15_suppl; p. e21196
• Main Authors: Serna, Roberto, Sanchez, Alfredo, De Julian, Maria, García Girón, Carlos, Domine, Manuel, Blasco, Ana, Sanchez Torres, Jose Miguel, Oramas, Juana, Bosch-Barrera, Joaquim, Sala, Maria Angeles, Sereno, Maria, Ortega, Ana Laura, Chara Velarde, Luis Enrique, Hernandez, Berta, Padilla, Airam, Coves, Juan, Jantus Lewintre, Eloisa, Molina-Vila, Miguel Angel, Romero, Atocha, Provencio-Pulla, Mariano
• Format: Journal Article
• Language: English
• Published: 20.05.2021
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2021.39.15_suppl.e21196

Abstract only e21196 Background: Non-small cells lung cancer (NSCLC) patients treated with Tyrosine Kinase Inhibitors (TKI) at first-line ultimately develop disease progression after 10 to 14 months. Mechanisms underlying TKI-resistance are not complete understood. Tumor re-biopsy is often unfeasible for NSCLC patients and liquid biopsy is a suitable alternative in identify mechanism by which tumors progress. Methods: 113 plasma samples were collected from advanced stage EGFR positive NSCLC patients upon disease progression according to RECIST V1.1. cfDNA NGS profiling was carried out using the Oncomine™ Pan-Cancer Cell-Free Assay and sequenced on an Ion GeneStudio S5 Plus System. Variant calling and annotation were performed with Torrent Suite and Ion Reporter (v5.16) software, respectively. In addition, we developed a bioinformatic pipeline, using RStudio for variant filtering. Results: Overall, 344 somatic variants were detected with an average number of variants per patient of 2.32 and a median Mutant Allele Frequency (MAF) of 0.83%. Most mutated genes were EGFR (63.72%), TP53 (60.18%), APC (16.81%), MAP2K1 (11.50%), PIK3CA (10.62%), FGFR3 (7.08%), KRAS (7.08%) and BRAF (6.19%). As expected, SNPs were the most frequent mutation type (72.67%), following by INDELs (24.41%) and CNVs (2.91%). We found high co-occurrence between MYC-GNA11, MYC-CCND2, HRAS-AR and EGFR-TP53 genes using Jaccard’s score (0.5, 0.5, 0.5 and 0.46, respectively). Within EGFR-mutated patients, 40% had T790M resistance mutation. Finally, we found KRAS mutations and missense PIK3CA mutations were mutually exclusive. Conclusions: Molecular profiling of liquid biopsies collected upon disease progression using NGS help to identify molecular mechanisms underlying treatment failure.