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Ctnnb1, axin1 and apc expression analysis in different variants of medulloblastoma

Grant number: 12/20910-9
Support Opportunities:Regular Research Grants - Publications - Scientific article
Duration: November 01, 2012 - April 30, 2013
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Sueli Mieko Oba Shinjo
Grantee:Sueli Mieko Oba Shinjo
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


OBJECTIVES: We investigated four components of the Wnt signaling pathway in medulloblastomas.BACKGROUND: Medulloblastoma is the most common malignant pediatric brain tumor. Wnt signaling is one of the activated signaling pathways in this kind of tumors. METHODS: Sixty one medulloblastoma cases were analyzed for b-catenin gene (CTNNB1) mutation, b-catenin protein immunostaining and expression of genes involved in Wnt signaling pathway. All data were correlated with histological subtypes and patient clinical information.RESULTS: CTNNB1 sequencing analysis resulted in 11 out of 61 medulloblastomas harboring missense mutations on residues 32, 33, 34 and 37 located at exon 3. These mutations alter the glycogen synthase kinase-3b phosphorylation sites, which participates in b-catenin degradation. No statistical differences were observed between mutation status and histological medulloblastoma type, age of patient and overall and progression free survival time. The nuclear ²-catenin accumulation, observed in 27.9% of cases, was not associated with the histological type, CTNNB1 mutation status or to tumor cell dissemination. The relative expression levels of genes which code for proteins involved in Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1) were also analyzed and no significant correlations was found. Large cells medulloblastoma variant presented a lower CTNNB1 relative expression than the other tumor variants. CONCLUSIONS: A small sunset of medulloblastoma carries CTNNB1 mutations with the consequent nuclear accumulation of ²-catenin. Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity variants, but not in large cell type of medulloblastoma. (AU)

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