Oligodendrogliomas are primary brain tumors with oligodendrocytic features that arise in adults and children. Although these cancers are relatively indolent in comparison to other primary brain tumors, they tend to occur in younger people and are difficult to treat, resulting in devastating loss of life. Developing deeper understanding of oligodendroglioma biology and creating new personalized therapies for this disease therefore represent crucial unmet clinical needs.
Over the past decade, cancer genome sequencing efforts have provided profound insights into genetic changes that characterize oligodendroglioma. Some of the genetic alterations commonly observed in adolescent and adult oligodendrogliomas are expected to have primary effects on cellular metabolism, including hotspot isocitrate dehydrogenase-1 (IDH1) mutations and loss of chromosomal arms 1p and 19q3, which harbor numerous metabolic genes including succinate dehydrogenase B (SDHB). Despite the likely role played by metabolic reprogramming in this disease, few studies have been devoted to characterizing the biochemical state of these tumors.
We hypothesize that systematic metabolite profiling of primary oligodendroglioma samples will reveal metabolic hallmarks that distinguish these gliomas from other primary brain tumors and from normal brain tissue. By building a large-scale metabolomics dataset that represents multiple histological and genotypic glioma subtypes as well as both pediatric and adult brain tumors, it may be possible to discover unappreciated oligodendroglioma-specific metabolic dependencies that point to new therapeutic opportunities. Furthermore, this metabolomics dataset would complement existing ‘omics’-level data and enable integrative analyses to be performed that unveil novel genotype-phenotype associations in oligodendroglioma. These associations may offer new and important insights into the molecular pathogenesis of this disease.
What are the goals of this project?
The goal of this project is to create a metabolic atlas of oligodendroglioma
What is the impact of this project?
Our studies are expected to reveal a metabolomic signature of oligodendrogliomas that form in children and adults, creating new ‘omics’ information related to this disease that can be shared with the broader brain tumor research community. Additionally, our findings will inform new hypotheses regarding the biochemical consequences of commonly mutated metabolic genes in oligodendroglioma. These consequences could create tumor-specific metabolic vulnerabilities poised for therapeutic exploitation.
Why the CBTN request is important to this project?
Oligodendrogliomas, especially those that arise in adolescents, are fairly rare brain tumors. As such, obtaining sufficient numbers of pediatric oligodendroglioma samples from sources other than the CBTN would be difficult and require years to collect in sufficient numbers if done prospectively. The samples requested from the CBTN are integral to our efforts to elucidate the biochemical landscape of oligodendroglioma and will uniquely accelerate our work in this area.
The Children's Brain Tumor Network will contribute to this project by providing tumor samples.
High-grade glioma/astrocytoma (WHO grade III/IV)
High-grade Gliomas (HGG) in children nearly always result in a dismal prognosis. Although novel therapeutic approaches are currently in development, preclinical testing has been limited, due to a lack of pediatric specific HGG preclinical models. These models are needed to help test the effective
Low-Grade astrocytomas are the most common cancer of the central nervous system in children. They represent a heterogeneous group of tumors that can be discovered anywhere within the brain or spinal cord. Although surgical resection may be curative, up to 20% of children still suffer from the eff