Identification and functional characterization of novel myc-regulated long noncoding rnas in group 3 medulloblastoma

The impact of protein-coding genes on cancer onset and progression is a well-establishedparadigm in molecular oncology. Nevertheless, unveiling the contribution of the noncoding genes--including long noncoding RNAs (lncRNAs)--to tumorigenesis represents a great challenge forpersonalized medicine, since they (i) constitute the majority of the human genome, (ii) are essentialand flexible regulators of gene expression and (iii) present all types of genomic alterations describedfor protein-coding genes. LncRNAs have been increasingly associated with cancer, their highlytissue- and cancer type-specific expression making them attractive candidates as both biomarkersand therapeutic targets. Medulloblastoma is one of the most common malignant pediatric braintumors. Group 3 is the most aggressive subgroup, showing the highest rate of metastasis at diagnosis.Transcriptomics and reverse genetics approaches were combined to identify lncRNAs implicatedin Group 3 Medulloblastoma biology. Here we present the first collection of lncRNAs dependenton the activity of the MYC oncogene, the major driver gene of Group 3 Medulloblastoma. Weassessed the expression profile of selected lncRNAs in Group 3 primary tumors and functionallycharacterized these species. Overall, our data demonstrate the direct involvement of three lncRNAsin Medulloblastoma cancer cell phenotypes