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Gene expression investigation in regions of chromosome gain in osteosarcoma

Grant number: 07/02693-2
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2007
Effective date (End): September 30, 2009
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Silvia Regina Caminada de Toledo
Grantee:Francine Tesser Gamba
Home Institution: Departamento de Morfologia. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Osteosarcoma (OS) is a malignant bone tumor derived of the primitive mesenchyme and has the highest incidence in young adults 15-25 years. The diagnosis is made based on histopathologic and radiologic aspects. The presence of metastasis at diagnosis is a prognostic factor with a strong impact in the overall survival for these patients. In Brazil, the incidence of patients metastatic at diagnosis is 21%, while in developed countries this number is around 10%. Metastatic patients and patients that have relapsed have bad prognosis. Recent clinical trials, attempting to improve outcome through intensification of therapy or incorporation of new agents but have generally not been successful. Drugs resistance and unfavorable clinical evolution have been observed in at least 50% of the patients. In such a scenario, increasing focus has been placed on to obtaining a greater understanding of the basic biology of OS, with the goal of using that information to improve treatment. Etiology of osteosarcoma still unknown and the specific nature of the events that lead to tumorigenesis remains a challenge in osteosarcoma. Most osteosarcomas display complex numerical and structural chromosomal abnormalities with significant cell-to-cell vatiantion and heterogeneity. Early studies already show rearrangement and recurrent gain in 1p35-p36, 17p and in chromosome 19. Identification of specific chromosomal regions involved in osteosarcoma will allow future detailed investigation of the affected regions looking for potential genes candidates that may play a role in the pathogenesis of osteosarcoma. Thus, 10 genes localized in such regions, described before were selected. The study strategy will be real time PCR (QRT-PCR) in the aim to correlate the expression of FGR, E2F2, MIG6 / ERRFI1 genes localized at 1p36, PRKMK4 / MAP2K4 / ERK kinase1, MAPK7 localized at 17p, RRAS, FOSB, PUMA, JUND, localized at 19 chromossome, looking for association between these genes expression and disease progression. Moreover, the expression of the MTHFR gene localized at 1p36 will be analyzed, and correlated with the response of metotrexato a drug choice for treatment of the osteosarcoma patients.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TESSER-GAMBA, FRANCINE; PETRILLI, ANTONIO SERGIO; DE SEIXAS ALVES, MARIA TERESA; GARCIA FILHO, REYNALDO JESUS; JULIANO, YARA; CAMINADA TOLEDO, SILVIA REGINA. MAPK7 and MAP2K4 as prognostic markers in osteosarcoma. HUMAN PATHOLOGY, v. 43, n. 7, p. 994-1002, JUL 2012. Web of Science Citations: 18.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.