Occurrence and Characteristics of Keap1-Mutations in Patients with Non-Small Cell Lung Cancer (Nsclc)

Abstract

ABSTRACT Aim: The Kelch-like ECH-associated protein 1 (KEAP1) suppresses the Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) under physiological conditions and therefore the antioxidative and anti-inflammatory effect during oxidative stress. Mutations in KEAP1 are described for diverse tumor entities with a relatively high frequency. Limited data is available on the clinical relevance, the exact frequency of occurrence and the association with specific characteristics of patients. This study was performed to characterize KEAP1-mutated NSCLC clinically and genetically. Methods: Tumor tissue collected from 446 patients within a regional screening network was analyzed for KEAP1 mutations using next-generation sequencing (NGS). Clinical, pathological and genetic characteristics of these patients are described and compared with a control group of patients without KEAP1 mutation. Results: So far, we identified 33 patients with KEAP1 mutations. Among these we found at least 19 different mutations, of which the majority was not previously described. KEAP1 mutations were not restricted to a special exon, and in 30 patients (90.9%), additional driver mutations in KRAS, FGFR1, STK11, ALK, DDR2, and NRAS could be detected, as well as mutations and polymorphisms in TP53. KEAP1 mutations occurred in both adenocarcinoma and squamous cell carcinoma histology. Results of the ongoing clinical characterization of the patients as well as the prognostic and predictive impact of KEAP1 mutations in a prospective cohort will be presented. Conclusions: Our data suggest a role of KEAP1 mutations as a cofactor in addition to classical driver mutations underlying the malignant phenotype of lung cancer cells. Further data analysis will reveal the role of these mutations for the outcome of these patients. Disclosure: All authors have declared no conflicts of interest.