Gallo, MarcoChan, Jennifer A. W.Hoffman, Mary2018-09-142018-09-142018-09-05Hoffman, Mary (2018). Characterizing the Genomic Heterogeneity of Pediatric Glioblastoma (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32913http://hdl.handle.net/1880/107737Brain tumors are currently the most common cause of cancer-related deaths among children. With a 5-year survival rate of 20%, pediatric glioblastoma (pGBM) is a lethal brain tumor with no effective treatment options. Although pathologically indistinct from its adult counterpart, recent work has shown that pGBMs diverge at both the genetic and transcriptional level from the adult malignancy. Genomic analyses have identified a recurrent mutation in H3F3A, but this lesion is only present in a fraction of patients and has not contributed to the advancement of effective therapies. Using a longitudinal collection of primary and recurrent pGBMs with matched germlines, I have described a molecularly heterogeneous disease with extreme tumoral evolution. Perhaps my most striking finding is the presence of potentially deleterious structural variants in the patient germlines. Together, these findings suggest a novel hereditary component to tumor etiology which has not been previously described in this malignancy.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Cancerbrain cancerpediatric glioblastomagenomic heterogeneitywhole-genome sequencingBiology--CellGeneticsBiology--MolecularBiochemistrymaster thesis10.11575/PRISM/32913