Fusion Genes As Therapeutic Targets in Malignant Pleural Mesothelioma
Location(s): United States
Malignant pleural mesothelioma (MPM) is a very aggressive and one of the worst human cancers. A median survival still remains at around 15% in MPM patients and no personalized targeted therapy is currently available. Several chromosomal alterations and deletions have been identified in MPM, such as deletion/inactivation of CDKN2A, NF2, and BAP1. Most of these mutations and deletions are inactivating events. Thus, it is important to identify oncogenic drivers causing MPM to develop therapeutic molecular targets. We have done copy number analysis of three of the most commonly deleted genes (CDKN2A, NF2, and BAP1) in around 60 MPM samples and have identified triple-negative (TN) MPM patients having no deletion in any of the three genes. In our preliminary studies, these TN MPM patients showed different genetic expression and deletion patterns than other samples with deletions. Novel fusion and tumor-specific isoform candidates were identified in TN MPM patients using genome wide microarray analysis. Thus, we hypothesize that these TN MPM patients have different genetic characteristics and novel oncogenic fusions may contribute to MPM development. We have two aims in this project. First, we will perform a transcriptome (RNA)-seq to identify our novel fusion and isoform candidates in TN MPM. Second, the identified fusions and tumor-specific isoform will be validated with RT-PCR and 5’-RACE methods. The success of this project may lead to the development of novel therapeutic target.