Análise do número de cópias dos genes IGFIR, SF1 e FGFR4 em tumores adrenocorticais de crianças e adultos / Analysis of copy number variations of IGF1R, SF1 and FGFR4 genes in adrenocortical tumors from children and adults

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

Introduction: A high incidence of adrenocortical tumors in children and adults has been observed in Southern and Southeastern regions of Brazil. Overexpression of IGF1R, SF1 and FGFR4 genes have been described in adrenocortical tumors. Despite of overexpression be a common event in several neoplasias, the molecular mechanism implicated in this upregulation remains unknown. Objectives: To determine the copy number of IGF1R, SF1 and FGFR4 genes in pediatric and adult adrenocortical tumors. Additionally, correlate with IGF1R, SF1 and FGFR4 gene and/or protein expression data as well as with the histological diagnosis and evolution of the adrenocortical tumors. Patients and methods: Sixty and four patients with adrenocortical tumors were selected for this study. All patients were submitted to clinical evaluation and surgical treatment. Eight normal adrenal glands obtained in renal surgery or autopsies were used as controls. The MLPA reactions were performed with the DNA extracted from adrenal gland tissues in order to determine the copy number of IGF1R, SF1 and FGFR4 genes. SYBR Green real-time PCR was carried out to confirm MLPA data for IGF1R and SF1 genes. Results: IGF1R amplification was detected by MLPA and confirmed by SYBR green real-time PCR in only one adrenocortical carcinoma. Additionally, other loci amplification was detected (IGFBP3, FGFR4 and NSD1) as well as for control probes, suggesting aneuploidy in this malignant tumor. SF1 amplifications were shown in 10 adrenocortical tumors (8 from children and 2 from adults). The SF1 mRNA levels were significantly higher in adrenocortical tumors associated with increased SF1 gene copies when compared with adrenocortical tumors without gene amplification. Moreover, all adrenocortical tumors with SF1 gene amplification showed a strong SF1 staining. Twelve FGFR4 locus amplifications (3 from children and 9 from adults) were demonstrated by MLPA. FGFR4 locus amplification and overexpression of this gene were significantly more related to carcinomas. Conclusions: IGF1R amplification is a rare event in adrenocortical tumors and it was not responsible for the IGF1R overexpression of pediatric and adult adrenocortical tumors. SF1 gene amplification was detected predominantly in pediatric adrenocortical tumors and was associated with gene and protein overexpression. FGFR4 locus amplification was demonstrated mainly in adult maligant adrenocortical tumors. FGFR4 amplification and upregulation were more associated to adrenocortical carcinomas. Oncogenes amplification represents an important molecular mechanism in adrenocortical tumorigenesis

ASSUNTO(S)

fator esteroidogênico 1 gene amplification receptor igf tipo 1 receptors fibroblast growth factor neoplasias do córtex-supra-renal receptores de fator de crescimento de fibroblastos adrenocortical neoplasias receptor igf type 1 amplificação de genes steroidigenis fator 1

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