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Analysis of somatic driver genes in pediatric medulloblastoma

Title: Analysis of somatic driver genes in pediatric medulloblastoma.
Name(s): Sanchez, Kevin, author
Type of Resource: text
Genre: Text
Bachelor Thesis
Date Issued: 2018-04-09
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Medulloblastoma is the most common malignant pediatric brain tumor. The early incidence of medulloblastoma and low prevalence of germline mutations suggest that somatic mutations have a significant effect on medulloblastoma development. This thesis focuses on the analysis of somatic driver genes to identify aberrant pathways contributing to the genetic architecture of medulloblastoma incidence. These signaling pathways were determined through gene set enrichment analysis on the medulloblastoma driver genes. Additionally, single nucleotide variant data was utilized to generate medulloblastoma’s mutational profile to understand the mutational processes that contribute to its development. In SHH-activated medulloblastoma, the contribution of somatic driver genes to the activation of the SHH pathway was inconclusive. In contrast, the Wnt signaling pathway in Wnt-activated medulloblastoma was significantly upregulated by somatic driver gene mutations. In Group 3 medulloblastoma, gain-of-function mutations in an inhibitor of pro-inflammatory cytokines, HIVEP3, could aid in explaining the poor prognosis of this subgroup. Group 4 medulloblastoma samples had driver gene mutations in molecules that may activate the Wnt pathway but inhibit the SHH pathway. Analysis of medulloblastoma’s mutational profile demonstrated an abundance of cytosine to thymine transitions. Decomposition of this profile into known mutational signatures revealed two significant mutational processes: spontaneous deamination of 5-methylcytosine and defective DNA mismatch repair. Understanding the genetic architecture of medulloblastoma through the analysis of somatic driver gene mutations and aberrant signaling pathways may help in revealing the molecular mechanisms of these tumors that ultimately assist in the development of drugs for targeted therapy.
Identifier: FSU_libsubv1_scholarship_submission_1523308354_0d88377b (IID)
Keywords: Medulloblastoma, Cancer, Biochemistry, Wnt, SHH, Mutational signatures, Gene set enrichment analysis
Persistent Link to This Record:
Use and Reproduction: Creative Commons Attribution (CC BY 4.0)
Host Institution: FSU

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Sanchez, K. (2018). Analysis of somatic driver genes in pediatric medulloblastoma. Retrieved from