MB-28: MicroRNA EXPRESSION IS HIGHLY SUBGROUP SPECIFIC IN MEDULLOBLASTOMA

Medulloblastoma (MB), the commonest malignant brain tumor of childhood, is divided into four tumor subgroups representing distinct clinical and molecular entities. MicroRNAs (miRNAs) are involved in carcinogenesis and tumor progression by regulating post-transcriptional gene expression. However, our understanding of the miRNA-mRNA regulatory network is incomplete. The aim of the study is to identify novel miRNA subgroup biomarkers and their target mRNAs for rapid and specific diagnosis and future targeted therapy. With this aim, integrated whole transcriptome mRNA and miRNA expression analysis was performed on primary tumor samples collected from 10 MB patients. 867 mature miRNAs were identified in at least a single MB sample, of them 462 were common to all 4 subgroups. 25 (2.5%) of all expressed miRNAs appeared to be significantly differentially expressed between the MB subtypes (FDR < 0.1). Namely, upregulation of hsa-miR-224-5p and hsa-miR-449c-5p was found exclusively among WNT, while downregulation of hsa-miR-135b-5p characterized SHH. Among groups 3 and 4, hsa-miR-20a-5p was upregulated or downregulated, respectively. RNA-seq from the same tumor samples identified 500 genes that vary between subtypes (q value <0.05), among which 69 (13.8%) have anti-correlated miRNA-mRNA interactions with the 25 detected miRNA biomarkers. The predicted mRNAs targets of these miRNAs are associated with different signaling pathways, known to have a role in MB biology. Our study demonstrates that miRNAs are readily detectible and are highly specific to distinct MB subgroups. Understanding the involvement of miRNAs and their targets in MB related signaling pathways may improve diagnosis and advance the development of targeted treatment for MB.