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Characterizing long non-coding RNAs as therapeutic targets in diffuse intrinsic pontine glioma
RNAs are intermediates between the DNA (which contains the instructions for cell functions) and the proteins (which carry out the cell functions). However, other types of RNAs exist which do not result in formation of proteins. Long non-coding RNAs (lncRNAs) are RNAs that are expressed in cells and are capable of interacting with other proteins to change how these proteins normally work. It is becoming increasingly evident that changes in these lncRNAs can participate in tumor formation and progression, thus representing a novel target for cancer therapy. We have recently performed whole-genome DNA sequencing of almost 200 Diffuse Intrinsic Pontine Gliomas (DIPGs) and high-grade gliomas, including a large number of pretreatment tumors collected on the recent DIPG-BATs clinical trial (which incorporated diagnostic biopsies for children with DIPGs). This analysis revealed almost 10% of all tumors to carry a rearrangement (a mutation that connects two pieces of DNA that should not normally be in contact) involving a specific lncRNA that has been previously implicated in cancers. In this proposal, we will examine the role this lncRNA plays to control DIPG growth. In addition, we will also use a genome-editing technology to identify other lncRNAs that are required for DIPG cells to grow. Taken together, these experiments will identify which lncRNAs might be targeted in novel therapeutic strategies for children diagnosed with these devastating tumors.