PI: Lionel Chow, Cincinnati Children’s Hospital Medical Center
Summary report, grand duration 2011-2013
Children who develop high-grade glioma (HGG) have a very poor prognosis. New and more effective treatment options are desperately needed to improve patient survival and quality of life. In order to better understand how these tumors grow, we are looking at a new class of genes called microRNAs. We are in the process of profiling the entire complement of this class of genes in order to uncover which ones are abnormally elevated or alternatively missing in tumors as well as in the blood of patients. Since microRNAs play an important role in determining which genes are expressed and at what levels, having information about microRNA expression will help us to understand more about HGG. This in turn, could lead to new ideas and approaches to treat these aggressive tumors. Earlier this year, an exciting discovery was made when a small number of very specific mutations in two related genes were found in a high proportion of pediatric HGG. The mutations were particularly prominent in a subset of patients with diffuse intrinsic pontine glioma (DIPG), a devastating subtype of HGG. Importantly, while the exact manner by which these mutations promote HGG growth is not yet known, the proteins that are affected are known to play an integral role in regulating overall gene expression. Therefore, as we move into the analysis phase of our microRNA expression data, it will be particularly interesting and important to look at the relationship between the presence or absence of this new class of mutations and the presence or absence of specific microRNAs in the tumor. The long term goal of our research is to identify new ways of treating children with HGG and hopefully to improve their outcome.