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Analysis of DICER1 gene in pediatric and adult adrenocortical tumors

Grant number: 12/21272-6
Support type:Regular Research Grants
Duration: April 01, 2013 - March 31, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Madson Queiroz Almeida
Grantee:Madson Queiroz Almeida
Home Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Ana Claudia Latronico Xavier

Abstract

Adrenocortical cancer accounts for 0.05-0.2% of all cancers, with an estimated incidence of 0.5-2.0/million/year in adults. Interestingly, the incidence of pediatric adrenocortical tumors is remarkably high in South and Southern Brazil, where it is estimated to be 10-15 times greater than the worldwide incidence. There are currently few therapeutic options for patients with adrenocortical cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. miRNA expression profile of human tumors has been characterized by an overall miRNA downregulation. It was recently demonstrated that escaping miRNA control in cancer cells due to Dicer downregulation may allow the phenotypic emergence of more aggressive genetic variants, accelerating cancer progression. DICER1 downregulation was caused by the over-expression of miR-103 e miR-107, which represented predictors of poor outcome and metastasis in breast cancer patients. Recently, DICER1 mutations in the RNase IIIb domain were found in 29% of nonepithelial ovarian tumors, predominantly in Sertoli-Leydig cell tumors (60%). These mutations were restricted to codons encoding metal-binding sites within the RNase IIIb catalytic centers, which are critical for microRNA interaction and cleavage. Since adrenocortical tumors are also sterodoigenic lesions such as Leydig cell tumors and up to 12% of adrenocortical tumors are diagnosed before 1yr, which suggests an embryonic origin, we decided in this proposal to investigate DICER1 mutations in metal biding sites located at the RNase IIIb domain, and to study DICER1 and miR-103/107 expression in 91 pediatric and adult adrenocortical tumors. To achieve these goals, we will employ the real-time PCR, automated sequencing and imunohistochemistry. (AU)

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)
VIEIRA DE SOUSA, GABRIELA RESENDE; RIBEIRO, TAMAYA C.; FARIA, ANDRE M.; MARIANI, BEATRIZ M. P.; LERARIO, ANTONIO M.; ZERBINI, MARIA CLAUDIA N.; SOARES, IBERE C.; WAKAMATSU, ALDA; ALVES, VENANCIO A. F.; MENDONCA, BERENICE B.; FRAGOSO, MARIA CANDIDA B. V.; LATRONICO, ANA CLAUDIA; ALMEIDA, MADSON Q. Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma. ONCOTARGET, v. 6, n. 26, p. 22724-22733, SEP 8 2015. Web of Science Citations: 7.
DE SOUSA, G. R. V.; SOARES, I. C.; FARIA, A. M.; DOMINGUES, V. B.; WAKAMATSU, A.; LERARIO, A. M.; ALVES, V. A. F.; ZERBINI, M. C. N.; MENDONCA, B. B.; FRAGOSO, M. C. B. V.; LATRONICO, A. C.; ALMEIDA, M. Q. DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1 in Tumorigenesis. Hormone and Metabolic Research, v. 47, n. 9, p. 656-661, AUG 2015. Web of Science Citations: 5.
FARIA, ANDRE M.; SBIERA, SILVIU; RIBEIRO, TAMAYA C.; SOARES, IBERE C.; MARIANI, BEATRIZ M. P.; FREIRE, DANIEL S.; DE SOUSA, GABRIELA R. V.; LERARIO, ANTONIO M.; RONCHI, CRISTINA L.; DEUTSCHBEIN, TIMO; WAKAMATSU, ALDA; ALVES, VENANCIO A. F.; ZERBINI, MARIA CLAUDIA N.; MENDONCA, BERENICE B.; FRAGOSO, MARIA CANDIDA B. V.; LATRONICO, ANA CLAUDIA; FASSNACHT, MARTIN; ALMEIDA, MADSON Q. Expression of LIN28 and its regulatory microRNAs in adult adrenocortical cancer. Clinical Endocrinology, v. 82, n. 4, p. 481-488, APR 2015. Web of Science Citations: 14.

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