Csig-22. Identification and Characterization of Novel Transcribed Ultra-Conserved Regions as Long Non-Coding Rnas in Medulloblastoma

Medulloblastoma is the most common malignant pediatric brain tumor. While survival has improved with molecular subgrouping, children who undergo standard of care treatments frequently experience permanent neurological deficits and face poor prognoses. This work investigates the role of “Transcribed Ultra-Conserved Regions” (TUCRs) in medulloblastoma about which there is no published literature. TUCRs represent a distinct group of 481 putative lncRNAs that are 100% conserved across human, mouse, and rat genomes. These elements change 20 times slower than the average genomic region and are therefore under intense negative selection. Since their discovery, TUCRs have remained exceedingly underexamined within cancer research. We hypothesize that TUCRs play critical roles in medulloblastoma which will lead to the development of targeted therapies for medulloblastoma of which there are none approved. We used RNA-sequencing and differential gene expression analysis of medulloblastoma tumors compared to normal cerebellum to investigate TUCR dysregulation followed by Kaplan-Meier correlation to survival analysis. This revealed significant TUCR dysregulation and identified numerous TUCRs whose expression was significantly correlated with overall survival. Generation and application of a multifaceted scoring and prioritization system determined the top intergenic TUCRs in medulloblastoma. Experimentation using medulloblastoma cell lines indicated significant dysregulation of these TUCRs and functional assays showed that uc.303 inhibits cell proliferation and promotes cell invasion. We are currently investigating the functions of these select TUCRs in medulloblastoma. Altogether, our work investigates the oncogenic and tumor suppressive nature of TUCRs. It is the first study of TUCRs in medulloblastoma and will significantly advance our basic understanding of TUCRs.