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El destino intracelular y extracelular del ADN y la cromatina de los micronúcleos determina su patogenicidad
Micheline Kirsch-Volders1, Michael Fenech2, Miroslav Mišík3
1Laboratory for Cell Genetics, Department Biology, Faculty of Sciences and Bio-engineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, Brussels 1050, Belgium.
Mutation research. Reviews in mutation research
|September 3, 2025
Resumen
Los micronúcleos (MN) y su ADN son actores clave en la inestabilidad genómica y la inflamación. El ADN derivado de MN en el ADN libre de células circulantes (cfDNA) puede ofrecer nuevos conocimientos para el diagnóstico y el monitoreo de enfermedades.
Área de la Ciencia:
- La genómica
- Biología molecular
- Descubrimiento de biomarcadores
Sus antecedentes:
- El ADN libre de células en circulación (cfDNA) es un biomarcador vital no invasivo para el manejo de la enfermedad.
- El ADN citoplasmático contribuye a la inestabilidad genética y la inflamación, impulsando enfermedades como el cáncer.
- La naturaleza compleja del ADN intracelular y extracelular plantea desafíos analíticos.
Objetivo del estudio:
- Revisar el origen, la composición y el destino de los micronúcleos (MN) y su ADN.
- Para resaltar el papel de MN en la inestabilidad genómica y la activación inmune.
- Explorar las implicaciones del ADN derivado de MN para el desarrollo de biomarcadores de cfDNA.
Principales métodos:
- Síntesis de las pruebas actuales sobre la biología de la MN.
- Examen de la formación de MN, resultados intracelulares y ruptura de la envolvente.
- Exploración de los mecanismos de extrusión de MN y su impacto en el cfDNA.
Principales resultados:
- Los micronúcleos (MN) se forman a partir de fragmentos cromosómicos o cromosomas enteros.
- La ruptura de MN puede conducir a cromotripsis y inflamación mediada por cGAS-STING.
- MN o su ADN pueden ser extrudidos, influyendo en la composición y detección de cfDNA.
Conclusiones:
- El ADN y la cromatina derivados de MN están relacionados con la inestabilidad genómica y la progresión de la enfermedad.
- La biología MN ofrece información sobre la composición del cfDNA y el potencial de los biomarcadores.
- Se necesita más investigación sobre el aclaramiento de MN, el origen tisular y la detectabilidad en plasma.
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