Perfil de alterações genômicas em angiofibromas nasofaringeos juvenis
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Data
2008-07-28
Autores
Silveira, Sara Martorelli da [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O Angiofibroma Nasofaríngeo Juvenil (ANJ) é um tumor vascular e localmente invasivo e, por ocorrer predominantemente em adolescentes do sexo masculino, sugere-se que é uma neoplasia hormônio dependente. Embora seja um tumor bastante raro e de crescimento lento, o ANJ pode progredir para lesões avançadas, tendo sérias seqüelas para seu portador. Por estas razões, este tumor pouco relatado em literatura é um modelo interessante para análise de alterações genômicas e moleculares. Neste estudo foi utilizada a metodologia de hibridação genômica comparativa de alta resolução (HR-CGH) para a triagem de perdas e ganhos cromossômicos em 18 amostras de ANJs. Em nove destes casos, as células endoteliais e os fibroblastos foram isolados por microdissecção a laser e analisados separadamente por HRCGH. As regiões genômicas consistentemente alteradas foram investigadas em bancos de dados com o objetivo de identificar genes candidatos que pudessem estar relacionados com a etiologia destes tumores. Baseando-se na função e localização, dois genes foram selecionados e validados pela análise de expressão quantitativa em tempo real (qRT-PCR) em 18 amostras de ANJs. Entre os 18 ANJs, foram detectadas 281 regiões genômicas preferencialmente alteradas. A análise dos componentes celulares isolados revelou aproximadamente 90 regiões cromossômicas significativamente alteradas. Os ganhos genômicos foram mais prevalentes nas células endoteliais do que nas células estromais. Regiões consistentes de perdas e ganhos comuns entre as mesmas amostras microdissecadas (dois componentes isolados) e não microdissecadas revelaram concordância de 58%. A análise individualizada dos dois componentes celulares presentes no tumor mostrou diversas regiões significativamente alteradas incluindo 3p, 4q, 8q, 16q e X. Ganhos em 8q21-q22, 4q25 e Xq11.2-q12 foram detectados nos dois componentes...
Juvenile Nasopharyngeal Angiofibroma (JNA) is a locally invasive vascular tumor that occurs predominantly in male adolescents, suggesting that the tumor may be hormonedependent. Although this tumor is rare and presents a slow growth, JNA may evolve to advanced lesions, resulting in severe consequences for the patient. For these reasons, this tumor, which is scarcely reported on literature, is an interesting subject to research for genomic and molecular alterations. In this study, the high-resolution comparative genomic hybridization (HR-CGH) methodology was performed to screening of genomic gains and losses in 18 JNA samples. In nine out of 18 cases, the endothelial and stromal components were isolated by laser microdissection and they were analyzed by HR-CGH separately. The consensus abnormal genomic regions were investigated using databases to identify potential candidate genes which could be associated to JNA etiology. According to the function data, two potential genes were selected and validated in a second group of 18 JNA samples by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) method. In 18 JNA cases, were observed 281 significant altered genomic regions. The differential analysis of the endothelial and stromal components identified about ninety significant altered chromosomal regions. The genomic gains were more prevalent in endothelial than fibroblasts cells. The comparison between non-microdissected and microdissected sample HR-CGH data showed concordance in 58% genomic regions. The individual analysis of each cellular component identified many chromosome regions significantly altered, including 3p, 4q, 8q, 16q e X. Gains in 8q21-q22, 4q25 and Xq11.2-q12, were detected in both endothelial and fibroblastic components. Genomic losses on 16q22.1 were frequently observed in stromal cells (8/9 cases) and 3p21 gain in endothelial cells (4/9 cases)... (Complete abstract click electronic access below)
Juvenile Nasopharyngeal Angiofibroma (JNA) is a locally invasive vascular tumor that occurs predominantly in male adolescents, suggesting that the tumor may be hormonedependent. Although this tumor is rare and presents a slow growth, JNA may evolve to advanced lesions, resulting in severe consequences for the patient. For these reasons, this tumor, which is scarcely reported on literature, is an interesting subject to research for genomic and molecular alterations. In this study, the high-resolution comparative genomic hybridization (HR-CGH) methodology was performed to screening of genomic gains and losses in 18 JNA samples. In nine out of 18 cases, the endothelial and stromal components were isolated by laser microdissection and they were analyzed by HR-CGH separately. The consensus abnormal genomic regions were investigated using databases to identify potential candidate genes which could be associated to JNA etiology. According to the function data, two potential genes were selected and validated in a second group of 18 JNA samples by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) method. In 18 JNA cases, were observed 281 significant altered genomic regions. The differential analysis of the endothelial and stromal components identified about ninety significant altered chromosomal regions. The genomic gains were more prevalent in endothelial than fibroblasts cells. The comparison between non-microdissected and microdissected sample HR-CGH data showed concordance in 58% genomic regions. The individual analysis of each cellular component identified many chromosome regions significantly altered, including 3p, 4q, 8q, 16q e X. Gains in 8q21-q22, 4q25 and Xq11.2-q12, were detected in both endothelial and fibroblastic components. Genomic losses on 16q22.1 were frequently observed in stromal cells (8/9 cases) and 3p21 gain in endothelial cells (4/9 cases)... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Genética, Aparelho respiratorio - Tumores - Aspectos genéticos, Nariz, Faringe, Tumors Genetic aspects
Como citar
SILVEIRA, Sara Martorelli da. Perfil de alterações genômicas em angiofibromas nasofaringeos juvenis. 2008. 127 f. Dissertação (mestrado) - Universidade Estadual Paulista, Instituto de Biociências de Botucatu, 2008.