Creating NF1/CDKN2A/ATRX Models for NF1 Associated High Grade Glioma

Even though the frequency of high grade glioma (HGG) is low, they have an disproportional effect on the morbidity of NF1 patients. Recent studies have identified additional mutations that might be involved in NF1 HGG formation and progression from benign gliomas to malignant gliomas. Unfortunately, accurate in vitro cell models and in vivo mouse models for NF1 associated high-grade gliomas that incorporate this new mutation data do not exist, hampering our ability to really understand what drives these NF1 associated HGG. It is exactly this mechanistic understanding that will eventually allow us to develop rational therapies. This projects aims to develop accurate in vitro and in vivo models for NF1-associated HGG with mutations in the NF1, ATRX and CDKN2A genes. Dr. Thomas Raedt and his team will also analyze our newly developed cell lines and mice to discover how these genes cooperate exactly to form HGG. These tractable models, together with the team’s unique expertise in dissecting complex mechanisms of tumor formation and preclinical testing form a powerful combination to better understand, therapeutically target and help patients with NF1 associated HGG.