Identification of Germline Modifiers of Neurofibromatosis Type 1 Tumors
Principle Investigators: Nancy Ratner, PhD, & Carlos Prada, MD
Twin studies suggest that germline modifiers of neurofibromatosis type 1 (NF1) disease exist. We have identified potential modifiers of peripheral nerve sheath tumors (neurofibromas) and have extensive data supporting the action of the gene ATM as one such modifier gene. Cincinnati Children’s large, well-characterized NF1 patient population will allow us to use whole exome sequencing (WES) to study the genomes of NF1 patients with and without defined numbers of peripheral nerve tumors called neurofibromas, and with and without optic pathway glioma, a type of eye tumor, at specific locations. The analysis will use our novel approach of identification of diverse variants within specific genes.
Our research will test the hypothesis that variants are de novo (appearing sporadically) or inherited from a parent without NF1 gene mutation. We also will collect DNA from parents / siblings of NF1 patients with identified variants. We will develop a database to be mined for genes that modify additional NF1 phenotypes and provide data to support an upcoming R01 submission focused on NF1 modifier gene functions. The potential outcomes of our study are identification of genes that contribute to patient phenotypes for risk stratification, and identification of targetable therapeutic pathways.