P2.03b-036 Analysis of Potentially Targetable Mutations in 821 Patients with Squamous cell Lung Cancer Undergoing Routine NGS-Based Molecular Diagnostics: Topic: Biomarkers

Molecular multiplex diagnostics is increasingly integrated now in routine diagnostics of lung adenocarcinoma (LAD). Although targetable aberrations are predominantly found in LAD, they have also been reported in squamous cell lung carcinoma (SQLC). We here present results of routine molecular multiplex diagnostics of advanced stage SQLC obtained within the German Network Genomic Medicine (NGM) and compare them with results reported previously in early stage SQLC in The Cancer Genome Atlas (TCGA) LUSC cohort. Tumor biopsies of 821 patients consecutively diagnosed within NGM were analyzed with next-generation parallel sequencing (NGS). The panel consisted of 102 amplicons and 14 genes: KRAS, PIK3CA, BRAF, EGFR, ERBB2, NRAS, DDR2, TP53, ALK, CTNNB1, MET, AKT1, PTEN and MAP2K1. In subsets of patients, fluorescence in-situ hybridization (FISH) was performed for amplification detection of FGFR1 and MET. We queried the TCGA dataset with respect to the panel used and compared the findings. For NGM patients, therapy and outcome are also reported. In addition to the expected frequencies of TP53, DDR2, PTEN and PIK3CA mutations, we detected EGFR mutations in 3.2% and BRAF mutations in 1.8%. Unlike the TCGA dataset, where the frequencies were 2.8% and 3.9%, respectively, the detected mutations in the NGM cohort included also activating targetable mutations (i.e., EGFR del19 and L858R, and BRAF V600E). FISH data revealed presence of MET amplification in 14.2% and of FGFR1 amplification in 20.0%. The association and correlation of these aberrations with clinical findings and prognosis as well as with PD-L1 expression status and mutational load will be presented. Our data give an overview on the presence and clinical characteristics of targetable mutations in advanced SQLC and show, that such mutations occur in a substantial amount of patients. Thus, molecular multiplex diagnostics might be indicated also in SQLC in order to use all therapeutic options available in these patients.