Abstract 4794: Kras mutation is associated with elevated myeloblastin activity in human lung adenocarcinoma

Abstract

Abstract Background Lung cancer is the leading cause of all cancer deaths worldwide with suboptimal prognosis and treatment options. Therefore we aimed to identify molecular characteristics with a predictive clinical utility that at the same time might represent novel therapeutic targets for human lung adenocarcinoma. Within this study we investigated KRAS mutations, a gene frequently mutated in lung adenocarcinoma and their association with enzymatic activities of members of the serine hydrolase superfamily, a large class of enzymes that have previously been linked to cancer. Methods Participating individuals underwent surgery for lung adenocarcinoma at the University Hospital Zurich between 2003 and 2006. Formalin fixed, paraffin embedded as well as snap-frozen lung adenocarcinoma samples were histologically reviewed by a pathologist. Mutation detection was performed via a custom service by Sequenom. Cell extracts derived from human snap-frozen biopsies were processed prior to mass spectrometric analysis as previously described to analyze serine hydrolase activities. Results Mutation analysis of 40 human lung adenocarcinoma specimens identified 4 patients (10%) harbouring a cysteine for glycine substitution at position 12 (G12C) in the KRAS gene. By employing two-sided unpaired t-test we found a statistical significant (p = 0.01) activity difference of the enzyme myeloblastin between patients harbouring a G12C mutation in the KRAS gene and patients harbouring no KRAS mutation. Conclusions The results of this study revealed that the activity of myeloblastin is significantly altered in lung adenocarcinoma biopsies harboring a KRAS gene mutation. Based on the results of this study we conclude that the combination of activity-based proteomics with mutational analysis is a valid approach for the discovery of novel biomarkers for human lung adenocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4794. doi:1538-7445.AM2012-4794