Impeding LIN28 Function in ATRT

Atypical teratoid rhabdoid tumors (ATRT) are a pediatric central nervous system (CNS) tumor that accounts for 30% of CNS tumors in patients younger than 3 years old. Genomic profiling has suggested molecular differences within ATRT, and three genomic subtypes have been described. (Group1-TYR, Group2A-SHH and Group2B-MYC) However, studies investigating ATRT have used a limited number of cell lines that have not represented all subtypes of this tumor. Better understanding of this complex disease and developing novel treatment approaches are desperately needed. The first aim of this specific project is to determine if pharmacological treatment of ATRT cell lines with difluoromethylornithine (DFMO) results in positive changes. The second aim of this project is to figure out if DFMO induced effects occur in all subtypes of ATRT, or if responses are subtype dependent. Information learned from these experiments may lead to the identification of biomarkers predictive of response to DFMO treatment and the development of clinical trials testing the efficacy of DFMO in ATRT patients.

Utilizing the resources provided by the Children’s Brain Tumor Network will greatly improve the impact of the experiments being undertaken in this project.