Cancer Susceptibility and Signaling Pathways in Low-Grade Brain Tumors

Background:

Hereditary cases of benign brain tumors are rare but they are devastating to affected children. Furthermore, knowledge gained by studying hereditary tumors can then be applied to better understand and treat non-familial cases. Our group discovered that defects in the fibroblast growth factor (FGF) pathway are involved in the development of brain tumors causing epilepsy. 

Project Goal:

In this study, we will inventory proteins specifically present in tumors with mutations in the gene FGFR1 to identify proteins or groups of proteins that participate directly in tumor formation. We hope to use this information to explore new cancer treatments as well as anti-epileptic drugs that target these proteins to help reduce seizures in affected children. We will also attempt to elucidate specific patterns of changes (mutations) responsible for the increased susceptibility to developing epileptic brain tumors in rare hereditary conditions called RASopathies known to have defects in the FGF pathway. 

In a parallel objective, we will extend our study to another type of brain tumors called Choroid Plexus Tumors that account for up to 20% of brain tumors in children younger than 2-years-old. Our first goal will be to discover the genetic causes of these tumors to help provide better classification and more accurate diagnoses among different subtypes. If we successfully identify a gene or pathway linked to cancer risk, we will follow the same experimental protocol as described for epileptic tumors above to investigate which proteins participate in tumor development and explore new treatment avenues.

Project Update 2021: 

This past year, our focus was to study the molecular changes produced by specific mutations seen in epileptic tumors called dysembryoplastic neuroepithelial tumors (DNETs). These tumors can appear in hereditarily or randomly. We are studying the molecular mechanisms driven by FGFR1 mutations that can help us design potential drug targets as well as deciphering the tumors profiles to integrate the biological mechanisms derived from the mutation and how those profile the tumor molecular features. We are also studying another type of low-grade brain tumor called choroid plexus papilloma and for which there is no known cause. We have identified a previously uncharacterized hereditary tumor syndrome featuring early onset schwannomas, choroid plexus papilloma and multinodular goiter caused by germline mutations in the microprocessor DGCR8 and are currently investigating the biological consequences of this mutation and defining the clinical consequences in carriers.