Medulloblastoma is the most common malignant paediatric brain tumour. Similar to other tumours, medulloblastoma pathogenesis involves abnormal regulation of several developmental growth pathways. As my thesis project, I studied the effects of aberrant HGF/MET signalling on medulloblastoma formation in two ways. In my first objective, I investigated the role that mutations play in activated HGF/MET signalling in medulloblastoma by searching for mutations in HGF/MET pathway genes, SPINT1, SPINT2, and MET, within primary medulloblastoma specimens. This screen identified several single nucleotide polymorphisms (SNPs) and two novel variations, one in each SPINT1 and SPINT2 genes.
In my second objective, I generated a transgenic mouse model with cerebellar-specific aberrant MET signalling. These mice developed extensive cerebellar abnormalities but formed no tumours. These results indicate that mutations in the HGF/MET pathway components alone are not sufficient to initiate medulloblastoma formation and must coincide with additional genetic insults to promote tumour formation, maintenance, and progression.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33766 |
| Date | 04 December 2012 |
| Creators | Onvani, Sara |
| Contributors | Rutka, James T. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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