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Interpretación de las mutaciones del cáncer utilizando un mapa multiscala de los sistemas de proteínas
Fan Zheng1,2, Marcus R Kelly1,2, Dana J Ramms2,3,4
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Science (New York, N.Y.)
|September 30, 2021
Resumen
La investigación del cáncer ahora mapea los sistemas de proteínas e identifica 395 bajo selección utilizando el mapa NeST. Esto revela cómo las mutaciones convergen en ensamblajes de proteínas, ayudando a comprender la evolución del cáncer.
Área de la Ciencia:
- Oncología y Biología de Sistemas
- Genómica y Proteómica
- Evolución del cáncer
Sus antecedentes:
- Comprender cómo las mutaciones genéticas afectan a los sistemas celulares como los complejos de proteínas es crucial en la investigación del cáncer.
- El mapeo de estos sistemas e identificación de los que están bajo selección mutacional presenta desafíos significativos.
- Las mutaciones dispares que afectan a los sistemas celulares comunes son clave para la progresión del cáncer.
Objetivo del estudio:
- Para crear un mapa completo de los sistemas de proteínas del cáncer.
- Desarrollar un modelo estadístico para la identificación de sistemas proteicos bajo la selección mutacional.
- Para revelar cómo diversas mutaciones tumorales convergen en ensamblajes de proteínas.
Principales métodos:
- Datos integrados de interacción multi-ómico para construir un mapa completo de los sistemas de proteínas del cáncer.
- Desarrolló un modelo estadístico unificado para identificar sistemas bajo selección mutacional.
- Analizaron 13 tipos de cáncer para identificar sistemas específicos afectados.
Principales resultados:
- Creado NeST (Sistemas anidados en tumores), un mapa de los sistemas de proteínas del cáncer.
- Se identificaron 395 sistemas específicos bajo selección mutacional en 13 tipos de cáncer.
- Se descubrió un complejo PIK3CA-actomiosina que inhibe la señalización y complejos de colágeno que promueven la proliferación.
Conclusiones:
- El mapa NeST integra procesos canónicos y nuevos descubrimientos en la evolución del cáncer.
- Los sistemas identificados sirven como potenciales biomarcadores clínicos, implicando 548 genes.
- Convergencia demostrada de mutaciones tumorales dispares en conjuntos de proteínas en varias escalas.
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