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Adriano de Paula Sabinohttp://lattes.cnpq.br/2875593207169323Luci Maria Sant'Ana DusseKarina Braga Gomes BorgesAna Paula Lucas Motahttp://lattes.cnpq.br/3224986932820123Fabiana Kalina Marques2024-01-10T12:24:37Z2024-01-10T12:24:37Z2023-03-03http://hdl.handle.net/1843/62533As neoplasias mieloides compreendem subtipos distintos de neoplasia hematológica, com características clínicas, genéticas e prognósticos diferentes. O conhecimento das bases genéticas das neoplasias mieloides tem aumentado rapidamente, sobretudo após o desenvolvimento do sequenciamento de nova geração. Estudos demonstram que semelhanças genéticas entre doenças morfologicamente tão distintas estão associadas à presença de variantes recorrentes afetando vias celulares agrupadas em categorias funcionais. Desta forma, foi avaliado a desempenho analítico do painel OncomineTM Myeloid, que permite a pesquisa de variantes em 40 genes alvos, fusões gênicas envolvendo 29 genes drivers e análise de expressão relativa de cinco genes, por sequenciamento de nova geração. Dentre as 34 amostras clínicas sequenciadas, em 29 (85,2%) foi detectada pelo menos uma variante. Foram detectadas um total de 63 variantes: 33 variantes de nucleotídeo único, 24 indels e seis fusões gênicas. Os genes mais frequentemente mutados em nossa coorte foram TET2, IDH2, FLT3 e ASXL1. Foi observada diferença na expressão gênica para os genes BAALC e WT1 quando comparados os grupos de leucemia mieloide aguda, neoplasia mielodisplásica e neoplasia mieloproliferativa. Foi observada diferença na relação plaqueta-linfócitos quando comparados os três grupos. Foi observada diferença na sobrevida quanto à presença de variantes nos genes FLT3 e TP53, e quanto ao número de variantes detectadas por amostra. O painel OncomineTM Myeloid demonstrou alta sensibilidade, especificidade e reprodutibilidade na detecção de variantes relevantes para a investigação das neoplasias mieloides. Este estudo demonstrou a relevância da avaliação do perfil molecular nas neoplasias mieloides por painéis de NGS para o diagnóstico e estratificação de risco destas doenças, sobretudo na leucemia mieloide aguda e neoplasia mielodisplásica. Estudos adicionais são necessários para melhor avaliar a relevância das análises de expressão dos genes avaliados, assim como das relações plaqueta-linfócito, neutrófilo-linfócito e monócito-linfócito para o diagnóstico e prognóstico das neoplasias mieloides.Myeloid neoplasms comprise biologically distinct subtypes of hematologic malignancy, with different clinical, genetic, and design features. Knowledge of the genetic basis of NMs has increased rapidly, especially after the development of next-generation sequencing. Studies demonstrate that genetic similarities between morphologically distinct diseases are associated with the presence of recurrent variants affecting cellular pathways grouped into functional categories. In this way, the analytical performance of the OncomineTM Myeloid panel was evaluated, which allows the search for variants in 40 target genes, gene fusions involving 29 driver genes, and analysis of the relative expression of five genes, by nextgeneration sequencing. Among the 34 sequenced clinical samples, 29 (85.2%) identified at least one variant. A total of 63 variants were detected: 33 single nucleotide variants, 24 indels and six gene fusions. Our cohort's most frequently mutated genes were TET2, IDH2, FLT3, and ASXL1. There was a difference in gene expression for the BAALC and WT1 genes when compared to the acute myeloid leukemia, myelodysplastic neoplasm, and myeloproliferative neoplasm groups. A difference was observed in the platelet-lymphocyte ratio when comparing the three groups. A difference in survival was observed in the cohort regarding variants in the FLT3 and TP53 genes and the number of variants detected per sample. The OncomineTM Myeloid panel demonstrated high sensitivity, specificity, and reproducibility in the detection of variants relevant to the investigation of myeloid neoplasms. This study demonstrated the relevance of molecular profiling in myeloid neoplasms by next-generation sequencing panels for the diagnosis and risk stratification of these diseases, especially in acute myeloid leukemia and myelodysplastic neoplasm. Additional studies in larger samples are needed to better evaluate the contribution of gene expression analyses and the platelet-lymphocyte, neutrophil-lymphocyte, and monocytelymphocyte ratios for the diagnosis and prognosis of myeloid neoplasms.Outra AgênciaporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Análises Clínicas e ToxicológicasUFMGBrasilFARMACIA - FACULDADE DE FARMACIAneoplasias mieloidessequenciamento de nova geraçãoValidação e aplicação do sequenciamento de nova geração para pesquisa de variantes genéticas em neoplasias mieloides e relação com o prognóstico da doença.Validation and application of next-generation sequencing for the detection of genetic variants in myeloid neoplasms and its relationship with disease prognosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALTese final_correçao pos banca_Fabiana Kalina Marques.pdfTese final_correçao pos banca_Fabiana Kalina Marques.pdfapplication/pdf3831950https://repositorio.ufmg.br/bitstream/1843/62533/1/Tese%20final_corre%c3%a7ao%20pos%20banca_Fabiana%20Kalina%20Marques.pdfef38edb72edf01e80bc1757bcf681655MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/62533/2/license.txtcda590c95a0b51b4d15f60c9642ca272MD521843/625332024-01-10 09:24:38.182oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2024-01-10T12:24:38Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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