Pesquisa por novos biomarcadores genéticos em gliomas de alto grau
DOI:
https://doi.org/10.17533/udea.acbi.v41n111a01Palavras-chave:
diagnóstico, genética, pronóstico, reparación del ADN, sangre, valor predictivo de las pruebasResumo
Os gliomas de alto grau são os tumores cerebrais mais comuns do sistema nervoso central (SNC); têm sobrevida média de apenas 18 meses, principalmente devido à resistência a diferentes estratégias terapêuticas. Até o momento, o único tratamento que conseguiu aumentar em alguns meses a sobrevida dos pacientes com esses gliomas é o protocolo de Stupp et al. (2005), que consiste em cirurgia pareada com adjuvante temozolamida (TMZ) e radioterapia (RT). Porém, apesar de prolongar a vida dos pacientes em até 18 meses, ainda carece de um valor prognóstico sensível e/ou específico.
Até o momento, existem apenas três marcadores moleculares de relevância clínica para esta doença; entretanto, o Instituto Nacional de Saúde dos Estados Unidos detectou um grupo de indivíduos ("respondedores excepcionais") que parecem ter uma sobrevida mais longa associada à hipermetilação do promotor do gene MGMT. Estudos recentes sugerem que existem outros fatores genéticos não descritos envolvidos no reparo de danos ao DNA em “respondedores excepcionais”.
Nesta revisão, o uso de reparo de DNA como biomarcador é sugerido quando pacientes com gliomas de alto grau são tratados com TMZ e RT genotóxicos. Além disso, três técnicas que permitem quantificar a instabilidade genética desses pacientes são detalhadas: detecção de Micronúcleos (MN) em linfócitos de sangue periférico pelo método de Fenech, detecção de MN em reticulócitos de sangue periférico por citometria de fluxo e Troca Cromátide Irmã (SCE).
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