P3.03-019 Molecular Characterization of Malignant Pleural Mesothelioma (MPM) by next Generation Sequencing: Topic: Mesothelioma Transitional

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite treatment. Chromosomal abnormalities are abundant in MPM and the most frequently mutated genes are BAP1, NF2 and CDKN2A. Expanded molecular profile in MPM may provide targetable molecular aberrations and improve treatment options for these patients (p). Thirty two MPM patients who progressed to standard chemotherapy underwent genetic tumor profiling in a molecular prescreening program at our institution between 2006 and 2015. Paraffin-embedded biopsies were used for the analysis. Mass detection (MassARRAY, Sequenom) including analysis of mutations in 25 oncogenes was used and since June 2014 multiplexed amplicon sequencing (AmpliSeq, Illumina) was implemented assessing mutations in 59 oncogenes. No patients received systemic treatment prior to obtain the tumor sample. Demographics: male/female (22/10); median age 60.5 (range 32-83 years); histology epithelial/no epithelial (24/8); PS 0/1 (15/17); stage III/IV (14/13). All patients were treated with chemotherapy. Sequenom was performed in 21 p and AmpliSeq in 11 p. Median follow up was 23.3 months and median overall survival (OS) for entire cohort was 30.2 months. The median OS for patients with epitheliod and no-epithelioid histology was 31.5 vs 21.4 months (p=0.033). Genetic alterations were detected in 5 patients (4 p with AmpliSeq and 1 p with Sequenom). The mutations detected were RNF43/ZNRF3 (2p), PI3KCA (1p), APC (1p) and P53 (1p). We did not identify significant association between mutations with histology, gender and clinical stage (p>0.05). Median survival for patients with mutations was not reached and for patients without mutations was 30.2 m (p=0.462). This study shows genetic alterations are not frequent in MPM and AmpliSeq detected more genetic alterations than Sequenom. With a limited number of patients, we suggest further investigations about the role of mutations in Wnt pathway in MPM.