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Texto completo SciELO Brasil
Ward, Laura S
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Id: biblio-887654
Autor: Batista, Fernando A; Marcello, Marjory A; Martins, Mariana B; Peres, Karina C; Cardoso, Ulieme O; Silva, Aline C D N; Bufalo, Natassia E; Soares, Fernando A; Silva, Márcio J da; Assumpção, Lígia V; Ward, Laura S.
Título: Diagnostic utility of DREAM gene mRNA levels in thyroid tumours
Fonte: Arch. endocrinol. metab. (Online);62(2):205-211, Mar.-Apr. 2018. tab, graf.
Idioma: en.
Projeto: Foundation for Research of the State of São Paulo (Fapesp).
Resumo: ABSTRACT Objective The transcriptional repressor DREAM is involved in thyroid-specific gene expression, thyroid enlargement and nodular development, but its clinical utility is still uncertain. In this study we aimed to investigate whether DREAM mRNA levels differ in different thyroid tumors and how this possible difference would allow the use of DREAM gene expression as molecular marker for diagnostic and/or prognosis purpose. Materials and methods We quantified DREAM gene mRNA levels and investigated its mutational status, relating its expression and genetic changes to diagnostic and prognostic features of 200 thyroid tumors, being 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesions [49 goiter and 50 follicular adenomas (FA)]. Results Levels of mRNA of DREAM gene were higher in benign (0.7909 ± 0.6274 AU) than in malignant (0.3373 ± 0.6274 AU) thyroid lesions (p < 0.0001). DREAM gene expression was able to identify malignancy with 66.7% sensitivity, 85.4% specificity, 84.2% positive predictive value (PPV), 68.7% negative predictive value (NPV), and 75.3% accuracy. DREAM mRNA levels were also useful distinguishing the follicular lesions FA and FVPTC with 70.2% sensitivity, 73.5% specificity, 78.5% PPV, 64.1% NPV, and 71.6% accuracy. However, DREAM gene expression was neither associated with clinical features of tumor aggressiveness, nor with recurrence or survival. Six different genetic changes in non-coding regions of DREAM gene were also found, not related to DREAM gene expression or tumor features. Conclusion We suggest that DREAM gene expression may help diagnose thyroid nodules, identifying malignancy and characterizing follicular-patterned thyroid lesions; however, it is not useful as a prognostic marker.
Descritores: Proteínas Repressoras/genética
RNA Mensageiro/genética
Neoplasias da Glândula Tireoide/diagnóstico
Biomarcadores Tumorais/genética
Proteínas Interatuantes com Canais de Kv/genética
Elementos Reguladores de Transcrição/genética
Proteínas Repressoras/metabolismo
RNA Mensageiro/metabolismo
Neoplasias da Glândula Tireoide/genética
Neoplasias da Glândula Tireoide/metabolismo
Biomarcadores Tumorais/metabolismo
Sensibilidade e Especificidade
Proteínas Interatuantes com Canais de Kv/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Estadiamento de Neoplasias
Limites: Humanos
Pessoa de Meia-Idade
Tipo de Publ: Estudo Comparativo
Responsável: BR1.1 - BIREME

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Texto completo SciELO Brasil
Costa, F. F
Sonati, M. F
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Id: lil-524320
Autor: Ribeiro, D. M; Zaccariotto, T. R; Santos, M. N. N; Costa, F. F; Sonati, M. F.
Título: Influence of the polymorphisms of the alpha-major regulatory element HS-40 on in vitro gene expression
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;42(9):783-786, Sept. 2009. graf, tab.
Idioma: en.
Projeto: FAPESP; . CNPq; . FAPESP.
Resumo: The α-MRE is the major regulatory element responsible for the expression of human α-like globin genes. It is genetically polymorphic, and six different haplotypes, named A to F, have been identified in some population groups from Europe, Africa and Asia and in native Indians from two Brazilian Indian tribes. Most of the mutations that constitute the α-MRE haplotypes are located in flanking sequences of binding sites for nuclear factors. To our knowledge, there are no experimental studies evaluating whether such variability may influence the α-MRE enhancer activity. We analyzed and compared the expression of luciferase of nine constructs containing different α-MRE elements as enhancers. Genomic DNA samples from controls with A (wild-type α-MRE) and B haplotypes were used to generate C-F haplotypes by site-directed mutagenesis. In addition, three other elements containing only the G→A polymorphism at positions +130, +199, and +209, separately, were also tested. The different α-MRE elements were amplified and cloned into a plasmid containing the luciferase reporter gene and the SV40 promoter and used to transiently transfect K562 cells. A noticeable reduction in luciferase expression was observed with all constructs compared with the A haplotype. The greatest reductions occurred with the F haplotype (+96, C→A) and the isolated polymorphism +209, both located near the SP1 protein-binding sites believed not to be active in vivo. These are the first analyses of α-MRE polymorphisms on gene expression and demonstrate that these single nucleotide polymorphisms, although outside the binding sites for nuclear factors, are able to influence in vitro gene expression.
Descritores: Regulação da Expressão Gênica/genética
Polimorfismo Genético/genética
Elementos Reguladores de Transcrição/genética
Limites: Humanos
Tipo de Publ: Estudo Comparativo
Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME

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