Clinical and molecular characteristics of non-small cell lung cancer in patients harboring CTNNB1 mutations.

8098 Background: Although somatic mutations of CTNNB1 in lung cancer have been described, there is still lack of information about prevalence, genetic variability, occurrence of additional aberrations and influence on outcome. This study was performed to analyze CTNNB1mutations in NSCLC genetically and clinically. Methods: Tumor tissue collected from 3885 patients within a regional screening network was analyzed for CTNNB1 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 CTNNB1 mutation. Results: We have identified 58 (1.5%) CTNNB1-mutated patients, whereof 51 have been analyzed so far. This cohort consisted of 32 female and 19 male patients. Adenocarcinoma histology was found in 42 patients (82.4%), but CTNNB1 mutations were also found in squamous cell and neuroendocrine carcinomas. 21 different CTNNB1 mutations were detected on exon 3, of which most are miss-sense mutations (49) besides 2 deletions. The most frequent mutations were S37F and S37C substitutions which each occurred in nine patients. Exclusive CTNNB1 mutations were only detected in five patients. In all remaining patients an additional driver mutation was found including mutations in KRAS, EGFR, BRAF, AKT, PIK3CA and ERBB2 as well as MET amplification, RET-KIF5b-Inversion, ROS1-fusion and mutations and polymorphisms of TP53. Conclusions: CTNNB1 mutations occur alone or in combination with other known oncogenic aberrations in NSCLC. Results of the ongoing clinical characterization of the patients as well as the prognostic and predictive impact of CTNNB1 mutations will be presented.