Identifying the Cells of Origins of Brain Tumors Using Somatic Mutations

Primary brain tumors are remarkably diverse, with more than 100 different defined types. The large diversity of brain tumors approximates the diversity of cell types in the normal brain, suggesting that each type of brain tumor corresponds to a different cell of origin. Definitive evidence that an individual brain tumor or type of tumor arises from a particular cell type requires a research method that allows for the tracing of single cells. Prior work by researchers on this project has developed methods for sequencing the entire genomes of single cells from the brain. This has revealed remarkable levels of mutations that could be used to trace the origins of brain tumors directly in human tissues. The goals of this project are to apply novel single-cell genome sequencing technologies for lineage tracing of pediatric brain tumors and to analyze genomic data generated by the Children’s Brain Tumor Network from pediatric tumors to profile mutational processes. The CBTN has already sequenced many pediatric brain tumors, which can immediately be used by researchers. Comprehensive genomic sequencing of these tumor types is not available anywhere else.