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1.
Prenat Diagn ; 31(13): 1270-82, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22034057

RESUMO

OBJECTIVE: To assess the feasibility of offering array-based comparative genomic hybridization testing for prenatal diagnosis as a first-line test, a prospective study was performed, comparing the results achieved from array comparative genomic hybridization (aCGH) with those obtained from conventional karyotype. METHOD: Women undergoing amniocentesis or chorionic villus sampling were offered aCGH analysis. A total of 1037 prenatal samples were processed in parallel using both aCGH and G-banding for standard karyotyping. Specimen types included amniotic fluid (89.0%), chorionic villus sampling (9.5%) and cultured amniocytes (1.5%). RESULTS: Chromosomal abnormalities were identified in 34 (3.3%) samples; in 9 out of 34 cases (26.5%) aCGH detected pathogenic copy number variations that would not have been found if only a standard karyotype had been performed. aCGH was also able to detect chromosomal mosaicism at as low as a 10% level. There was complete concordance between the conventional karyotyping and aCGH results, except for 2 cases that were only correctly diagnosed by aCGH. CONCLUSIONS: This study demonstrates that aCGH represents an improved diagnostic tool for prenatal detection of chromosomal abnormalities. Although larger studies are needed, our results provide further evidence on the feasibility of introducing aCGH as a first-line diagnostic test in routine prenatal diagnosis practice.


Assuntos
Transtornos Cromossômicos/diagnóstico , Hibridização Genômica Comparativa , Testes Genéticos/métodos , Cariotipagem/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Amniocentese , Amostra da Vilosidade Coriônica , Transtornos Cromossômicos/genética , Estudos de Viabilidade , Feminino , Humanos , Gravidez , Estudos Prospectivos
2.
J Clin Invest ; 115(4): 1068-81, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15761501

RESUMO

In papillary thyroid carcinomas (PTCs), rearrangements of the RET receptor (RET/PTC) and activating mutations in the BRAF or RAS oncogenes are mutually exclusive. Here we show that the 3 proteins function along a linear oncogenic signaling cascade in which RET/PTC induces RAS-dependent BRAF activation and RAS- and BRAF-dependent ERK activation. Adoptive activation of the RET/PTC-RAS-BRAF axis induced cell proliferation and Matrigel invasion of thyroid follicular cells. Gene expression profiling revealed that the 3 oncogenes activate a common transcriptional program in thyroid cells that includes upregulation of the CXCL1 and CXCL10 chemokines, which in turn stimulate proliferation and invasion. Thus, motile and mitogenic properties are intrinsic to transformed thyroid cells and are governed by an epistatic oncogenic signaling cascade.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Transdução de Sinais/fisiologia , Neoplasias da Glândula Tireoide/metabolismo , Proteínas ras/metabolismo , Animais , Comunicação Autócrina , Linhagem Celular , Proliferação de Células , Quimiocina CXCL1 , Quimiocina CXCL10 , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Perfilação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Invasividade Neoplásica , Proteínas Oncogênicas/genética , Proteínas de Fusão Oncogênica , Fenótipo , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas B-raf/genética , Ratos , Reprodutibilidade dos Testes , Glândula Tireoide/citologia , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Proteínas ras/genética
3.
Eur J Hum Genet ; 21(7): 725-30, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23211699

RESUMO

In this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Análise em Microsséries/métodos , Cariótipo Anormal , Transtornos Cromossômicos/etiologia , Feminino , Testes Genéticos , Humanos , Idade Materna , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
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