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Analysis of DICER1 gene in pediatric and adult adrenocortical tumors

Grant number: 13/09621-8
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2013
Effective date (End): July 31, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Madson Queiroz Almeida
Grantee:Gabriela Resende Vieira de Sousa
Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


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)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SOUSA, Gabriela Resende Vieira de. DICER1 and TARBP2 gene analysis in adult and pediatric adrenocortical tumors. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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