Using Whole Genome Bisulfite Sequencing to Identify Novel Therapeutic Targets in DIPG and ATRT

Diffuse intrinsic pontine gliomas (DIPG) and atypical teratoid rhabdoid tumors (ATRT) are epigenetically driven diseases with poor outcomes. Epigenetically driven means the growth and development of these tumors is driven by changes to gene expression that are not related to changes to DNA itself. The lack of druggable mutations and the cancer stem cell characteristics of these tumors are barriers to identifying drug targets, and new therapies to address these cancers are desperately needed. Recent work in a variety of cancer types, including ATRT and DIPG, has pointed to a critical role of epigenetic dysregulation such as altered DNA methylation. DNA methylation is the process by which methyl molecules are added to DNA molecules. Preliminary evidence confirms increased changes in DNA methylation as a fundamental property ATRT and DIPG. Researchers hypothesize that analysis of the genomic targets and biological pathways affected by methylation changes will identify gene regulatory networks responsible for the aggressive and therapy resistance types of ATRT and DIPG. Identifying such gene regulatory networks is critical in the search for new targets for therapy in the hardest to treat forms. The Children’s Brain Tumor Network contributed to this project by providing tumor DNA and cell lines from patients with DIPG and ATRT.