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The Role of Cell Adhesion Genes in the Pathogenesis of Medulloblastoma

Medulloblastoma is the most common pediatric brain tumour, yet many of the underlying genetic and epigenetic factors have yet to be discovered. After a genome wide screen of a large cohort of primary medulloblastomas, we discovered that many of the genes within the cell adhesion family are affected by either copy number loss and/or decreased expression unexplained by copy number change. This led us to believe that both genetic and epigenetic factors were affecting
this gene family. Through methylation-specific PCR, RT-PCR and high-throughput methylation status analysis, we have concluded that promoter CpG methylation plays a role in the expression of the PCDH10 protein in both medulloblastoma cell lines and primary tumours. Through functional validation with a stable cell line re-expressing PCDH10, I show that cell cycle and
proliferation remain unchanged but migration is decreased in cells with PCDH10 re-expression.
This suggests that PCDH10 has characteristics of a tumour suppressor in medulloblastoma.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/27544
Date02 June 2011
CreatorsBertrand, Kelsey C.
ContributorsTaylor, Michael
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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