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Changes in gene structure and protein expression of DVL1, DVL2 and DVL3 and transcription factors TCF1 and LEF1 in astrocytic brain tumors.

INTRODUCTION: Astrocytomas are the most common and deadliest form of primary brain tumors. Despite recent advances in diagnosis and therapies the prognosis and survival times remains poor. WHO classified astrocytomas into four clinical grades on the basis of their histology and prognosis. Wnt signaling pathway is one of the basic mechanisms of cell signaling as evidenced by its participation in a numerous processes in the cell. New insights showed that molecular key components of the wnt signaling pathway play crucial roles in the process of tumorigenesis of the central nervous system. HYPOTHESIS: DVL1, DVL2, DVL3, TCF1 and LEF1 are involved in the formation and malignant progression of astrocytic brain tumors and changes in the genes, and increased expression of the protein indicate a higher degree of malignancy. AIMS: We aim to investigate the incompletely understood role of Dishevelled (DVL) gene family, which is considered to be the central hub of wnt signaling. We also want to clarify the role that transcription factors TCF1 and LEF1, the central mediators of transcription of wnt signaling pathway, have in the development and progression of astrocytic brain tumors. MATERIALS AND METHODS: Scientific research will be conducted on tumor tissue, blood and paraffin sections of 80 patients with astrocytic brain tumors (15 pilocytic astrocitoma, 15 diffuse astrocytoma, 15 anaplastic astrocytoma, 35 glioblastoma). Genetic changes will be analysed by PCR/loss of heterozygosity (LOH)/microsatellite instability (MSI) methods using Spreadex electrophoresis. Protein expressions and localizations will be analyzed by immunohistochemistry. EXPECTED SCIENTIFIC CONTRIBUTION: Since the genetic profile of astrocytic brain tumors is still unclear the results of the proposed research could contribute to the elucidation of the mechanisms of initiation and progression of these tumors. More precise, the results could contribute to a discovery and better understanding of the role of DVL gene family and transcription factors TCF1 and LEF1 which could be responsable for the onset and progression of astrocytic brain tumors.

wnt signaling pathway; astrocytic brain tumor; DVL1; DVL2; DVL3; TCF1; LEF1

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