Developing Personalized (precision) Medicine Strategies to Optimize Pediatric Brain Tumor Management

Background
Brain tumors (low-grade gliomas) arising in children do not represent a single disease, but rather comprise a heterogeneous collection of distinct cancer subtypes. Our ability to more effectively manage children with brain tumors is therefore limited by an incomplete understanding of the factors that contribute to this heterogeneity. In the common cancer predisposition syndrome, neurofibromatosis type 1 (NF1), preliminary studies have suggested that the specific NF1 genetic mutation may be an underappreciated contributor to low-grade glioma formation, progression, and response to therapy.

Project Goal
To define the cause-and-effect relationship between the specific germline NF1 genetic mutation and low-grade glioma behavior, we propose to generate NF1-patient stem cell lines and mouse strains harboring different germline NF1 gene mutations. These proposed studies establish a new conceptual framework for developing and testing therapies tailored to specific children as an initial step towards personalized treatments for pediatric low-grade glioma.