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Cytogenetic and molecular investigations of metastatic osteosarcoma

Grant number: 07/02483-8
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): November 01, 2007
Effective date (End): February 29, 2012
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Silvia Regina Caminada de Toledo
Grantee:Carolina Salinas de Souza
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Osteosarcoma (OS) is a malignant bone tumor with high metastatic capacity, presenting with high incidence in children and adolescents. The main prognostic factors still are metastatic disease at diagnosis and histologic response to chemotherapic treatment, evaluated by the necrosis grade of the surgery specimen. Although osteosarcoma is the most common bone tumor in children, little is known about the genetic events involved in its genesis and progression, mainly those related with metastatic process. Thus, the present study will investigate cytogenetically the chromosomic region 12q13, place of MDM2 and OSTERIX genes, and the region 13q14 that contains RB1 and RANKL genes. Each region having a gene related with the cellular cycle regulation and another with osteoblastic and osteoclastic differentiation. The MDM2 gene acts negatively in the TP53-induced transcription of target genes. Moreover, RB1 gene is a important tumoral supressor, participating in the regulatory mechanisms during the cellular cycle progression of G1 to S phase. The recently identified OSTERIX gene plays an important role during the osteoblastic differentiation, and is also related with osteosarcoma tumor growth and metastasis. The RANKL gene has an equally important function, acting in the signalling pathways during the osteoclastic differentiation. Furthermore, expression profile of the mentioned genes will be analysed using Real Time PCR technique, together with CXCR4 and MMP9 genes that are strongly related with lung-specific metastasis mechanisms. So in this sense, the aim of this study will be the identification of genes involved in the metastatic mechanisms of osteosarcoma and its microenviroment. (AU)

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