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Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
La respuesta sinérgica a las mutaciones oncogénicas define la clase de genes críticos para el fenotipo del cáncer
Helene R McMurray1, Erik R Sampson, George Compitello
1Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642, USA.
Nature
|May 27, 2008
Resumen
El control sinérgico de la expresión génica mediante la cooperación de mutaciones oncogénicas es clave para la malignidad. Se dirigió a estos.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- El desarrollo del cáncer implica complejas mutaciones genéticas y expresión génica alterada.
- La identificación de genes críticos que impulsan el cáncer es un desafío.
- La transformación maligna requiere la cooperación entre las mutaciones oncogénicas.
Objetivo del estudio:
- Para investigar el papel de la modulación sinérgica de la expresión génica en el cáncer.
- Identificar genes críticos involucrados en la transformación maligna impulsada por mutaciones oncogénicas cooperantes.
- Explorar el control genético sinérgico como un objetivo para las intervenciones contra el cáncer.
Principales métodos:
- Análisis de patrones de expresión génica en células de colon murino y humano con pérdida de función de p53 y activación de Ras.
- Experimentos de perturbación genética para evaluar la contribución de los "genes de respuesta de cooperación" a la formación de tumores.
- Comparación de respuestas genéticas sinérgicas versus no sinérgicas en el desarrollo del cáncer.
Principales resultados:
- Una proporción significativa de genes controlados sinérgicamente por las mutaciones p53 y Ras son cruciales para las células malignas del colon.
- 14 de los 24 "genes de respuesta de cooperación" contribuyeron a la formación de tumores tras la perturbación.
- Los genes que responden sinérgicamente son más críticos para la malignidad que los que responden no sinérgicamente.
Conclusiones:
- El control sinérgico de la expresión génica por mutaciones oncogénicas es un mecanismo fundamental subyacente a la malignidad.
- La identificación de genes bajo control sinérgico ofrece una estrategia prometedora para descubrir nuevos objetivos de intervención contra el cáncer.
- Este estudio pone de relieve la importancia de la regulación genética cooperativa en la etiología del cáncer.
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