Molecular based approach to improve outcome for children and young adults with low grade glioma
Low grade glioma (LGG) is the most common brain tumor in humans under 40 y/o. As a result, LGG is a major cause of morbidity and mortality in children and adolescent/young adults (AYA). Childhood LGG have completely different molecular characteristics and outcome compared with their older (>40 y/o) adult counterparts. Many pediatric LGG are RAS/MAPK pathway driven and have excellent overall survival. In contrast, adult LGG harbor different alterations and inevitably transform to high grade glioma with a consequent poor outcome and aggressive therapy.
A huge knowledge gap exists regarding what is driving LGG in ~30% of children without canonical RAS/MAPK activating mutations. Furthermore, the prognostic significance of these alterations and their potential for targeted therapies is still unknown. The biggest challenge is in AYA-LGG where no data exist on the “cross-over” genetic alterations, i.e. pediatric type alterations occurring in adults and vice versa. As a result all are treated with toxic surgery/radiation approaches with poor outcome.
To address these issues, we established an international Canadian led LGG taskforce encompassing pediatric and adult centers in Canada and other countries. The overall goals of this project are to define the genetic landscape of childhood and AYA LGG, to determine their prognostic and therapeutic roles and to identify targets for novel therapies.