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Interpretación de los genomas del cáncer utilizando perturbaciones sistemáticas de la red del huésped por las
Orit Rozenblatt-Rosen1, Rahul C Deo, Megha Padi
1Genomic Analysis of Network Perturbations Center of Excellence in Genomic Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Nature
|July 20, 2012
Resumen
Las variaciones genómicas y los virus tumorales pueden causar cáncer al interrumpir las redes celulares del huésped. El análisis de los blancos de proteínas virales ayuda a identificar los genes que causan cáncer, mejorando nuestra comprensión del cáncer.
Área de la Ciencia:
- La genómica es la genómica.
- Biología de Sistemas Biología de Sistemas.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- El genotipo influye en la susceptibilidad a las enfermedades, pero comprender los vínculos genotipo-fenotipo requiere ver los fenotipos como propiedades de red.
- Distinguir las mutaciones que conducen al cáncer de las mutaciones pasajeras sigue siendo un desafío.
- Los virus humanos pueden causar fenotipos patológicos similares a las mutaciones.
Objetivo del estudio:
- Para probar si las variaciones genómicas y los virus tumorales causan cáncer a través de mecanismos relacionados.
- Para examinar las perturbaciones de la red del huésped causadas por las proteínas del virus del tumor del ADN.
- Para integrar los datos de perturbación viral con enfoques genómicos para la identificación de genes de cáncer.
Principales métodos:
- Examen sistemático de las perturbaciones de la red del interactoma y el transcriptoma del huésped inducidas por las proteínas del virus tumoral del ADN.
- Análisis integrado de datos de perturbaciones virales y datos genómicos.
- Comparación del análisis de la proteína viral objetivo con la genómica funcional y la catalogación de mutaciones tumorales.
Principales resultados:
- Las proteínas virales recablean las redes celulares del huésped, destacando vías como la señalización Notch y la apoptosis.
- El análisis sistemático de los blancos de proteínas virales identifica eficazmente los genes del cáncer.
- Este enfoque logra tasas de éxito comparables a las de la genómica funcional y la catalogación de mutaciones tumorales a gran escala.
Conclusiones:
- Las variaciones genómicas y los virus tumorales pueden compartir mecanismos que causan cáncer a través de la interrupción de la red.
- El análisis de los objetivos del huésped de las proteínas virales es un método poderoso para identificar los genes impulsores del cáncer.
- La combinación de estudios virales a nivel de sistemas con enfoques genómicos mejora la especificidad de la identificación de genes de cáncer y ayuda a comprender la base genética del cáncer.
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