Proteogenomic Identification of Structural Variations

Cancers commonly arise as the result of changes affecting the DNA sequence of cells. These changes include small variations such as insertions and deletions as well as structural variations (SVs) including deletions, duplications, and translocations. In addition to these, tumor specific alterations can also give rise to proteins not commonly found in normal tissues. Those abnormal proteins are formed when SVs cause two different genes to form a new gene called gene fusions. Tumor specific fusion proteins could be potential targets for immunotherapy and DNA SVs represent potential biomarkers detectable by liquid biopsy. Researchers on this project seek to identify genomic alterations by detecting peptides, the building blocks of proteins, present in tumor cells. They will do so by assessing RNA sequencing data, analysis that reveals the presence of RNA in a biological sample, provided through the Pediatric Brain Tumor Atlas. Researchers have also been provided with rare, high quality tissue and RNA samples by the Children’s Brain Tumor Network. The integration of protein-based and genomic data provides a more comprehensive view of the biological features that drive cancer. Using this approach, identified proteins can be studied individually to clarify their role in the origin and growth of tumors and leveraged for use in therapeutics.