Characterizing the Genomic Heterogeneity of Pediatric Glioblastoma
Date
2018-09-05
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Abstract
Brain 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.
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Keywords
Cancer, brain cancer, pediatric glioblastoma, genomic heterogeneity, whole-genome sequencing
Citation
Hoffman, 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/32913