Identification of microRNAs associated with aggressive choroid plexus tumor phenotypes
We previously demonstrated that combining histological approaches with a specific DNA methylation signature for choroid plexus carcinomas (CPCs) can help to differentiate aggressive tumors from those that are not life threatening. Herein, we investigate the role of miRNAs in choroid plexus tumorigenesis, given the well-established role of miRNAs in the pathogenesis of other cancers. We characterized miRNA expression (using miRNA-seq and miRNA PCR arrays) in different CPTs in order to establish which miRNAs can serve as predictive biomarkers for CPCs compared to the less aggressive forms - choroid plexus papilloma (CPP) and atypical choroid plexus papilloma (aCPP). We performed miRNA-seq on 35 CPTs and used real-time PCR for the validation. We identified significant differences in the miRNA expression profiles between CPCs and CPPs. The specific miRNA expression signature for CPCs revealed upregulation of several miRNA members of oncogenic miRNA clusters (miR-17-92, 106a-363, 183/96/182) and downregulation of the tumor suppressive miRNA 34b/c cluster. Our findings suggest that the identified miRNAs could serve as novel biomarkers for CPCs and that targeting these deregulated miRNAs could be a promising new treatment strategy for this aggressive form of CPTs where survival rates remain below 50%. Overall design: Determination of miRNAs expression in choroid plexus tumors