P10.15.A THE ROLE OF NONCODING RNAS IN THE PROGRESSION OF IDH-MUTANT ASTROCYTOMAS TO GRADE 4

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Abstract BACKGROUND Low grade IDHmutant astrocytomas are heterogeneous brain tumors that have a prognosis of 7-10 years. However, this prognosis is significantly worsened if the tumors progress to grade 4 astrocytomas. Noncoding RNAs, especially long noncoding RNAs and microRNAs, have been studied increasingly in the past years in various cancers including gliomas, and a general dysregulation was observed. The dysregulated RNAs were shown to regulate crucial disease processes, such as cell proliferation, apoptosis, and therapy resistance. Thus, several noncoding RNAs were identified as promising biomarkers and potential therapy targets, some of which are already being tested in clinical trials. Despite advances in the field, little is known about the role of noncoding RNAs in the progression of IDHmutant astrocytomas. MATERIAL AND METHODS We collected matched samples and clinical information from six IDHmutant astrocytoma patients before and after progression to grade 4 and subjected them to RNA- and small RNA-sequencing. We defined which microRNAs and long noncoding RNAs were significantly up- or downregulated upon progression. We also predicted the target genes of differentially expressed microRNAs utilizing machine learning algorithms and experimentally validated databases. The predicted targets were filtered for negative correlation in gene expression, and their biological relevance was assessed with gene set analysis and literature research. RESULTS We found 33 differentially expressed microRNAs upon progression, out of which 19 were up- and 14 were downregulated. A total of 443 negatively correlating targets were identified for the microRNAs (0-115 per microRNA). The target genes were associated with DNA repair, proliferation, and G-Protein coupled receptor signaling. Furthermore, we observed 19 up- and 14 downregulated lncRNAs within the differentially expressed genes. Six of them have been reported to be cancer-related, including known tumor-suppressors and lncRNAs known to promote cell proliferation, invasion and migration. CONCLUSION The study identified a number of noncoding RNAs associated with the progression of IDHmutant astrocytoma to grade 4. Further studies are needed to evaluate their potential to act as biomarkers or therapy targets.