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Analysis of TCF21/POD-1 transcriptor factor and cycle cells genes expression in adult adrenocortical tumors.

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Barbara dos Santos Passaia
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Claudimara Ferini Pacicco Lotfi; João Evangelista Bezerra Neto; Vanessa Morais Freitas
Advisor: Claudimara Ferini Pacicco Lotfi

The adrenocortical masses are mostly (70-80%) adrenocortical adenomas (ACA). Adrenocortical carcinomas (ACC) are scarce and have limited prognosis, with an incidence of 1-2 cases per million and high recurrence rate (70-80%). Despite adrenocortical tumors (ACT) are rare in Brazil the incidence of these tumors in children is about 10 times higher than the rest of the world, due to a mutation of the TP53 gene. Currently, the diagnosis of adrenocortical mass is carried through Weiss criteria that have limitations, so it is intensive the search for new molecular markers that facilitate the diagnostic of ACTs. TCF21/POD-1 is a transcription factor helix-loop-helix type expressed in mesenchymal-epithelial sites of interaction during embryonic development. In ACTs, POD-1 regulates the expression of endogenous SF-1 through binding the E-box sequence of SF-1 promoter region, and seems to be negatively relates with cell cycle regulatory genes such as BUB1B. BUB1B is a gene encoding a kinase-with important function during mitotic checkpoint. The expression of BUB1B is considered a prognostic factor in different types of tumors, including ACTs. Combined expression of BUB1B and PINK1 (ΔCtBUB1B - ΔCtPINK1) has been shown to be a good marker of survival in adults with ACC, whereas the PINK1 expression is reduced in the most aggressive ACC. We hypothesized that the POD-1 expression may have differential value in the diagnosis of adrenocortical masses, and that the analysis of the combined expression of POD-1, BUB1B and PINK1 may have differential value for the prognosis of patients with ACT. In this work were analyzed by PCRq Taqman probes the cDNA obtained from 130 tumor samples: 79 adults (44 ACAs and 35 ACCs), 35 children under 5 years old (27 ACAs and 8 ACCs) and 16 children 5-18 years of age (6 ACAs and 10 ACCs). Our results show that POD-1 and BUB1B has differential value in adult ACT, and the combined expression of POD-1 and BUB1B may have a prognostic value in patients with adult carcinoma. In addition, the combined expression of POD-1 and SF-1 might have diagnostic value in pediatric patients younger than 5 years. In summary, we conclude that experimental studies should be conducted to confirm the relationship between the genes studied, so that the results are solid enough to be used in the diagnosis and prognosis of adrenocortical tumors. (AU)

FAPESP's process: 13/23548-1 - Analysis of the expression of transcription factors Pod-1, SF-1, PINK1 and BUB1B in human adrenocortical tumors
Grantee:Barbara dos Santos Passaia
Support Opportunities: Scholarships in Brazil - Master