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Las firmas de mutación y selección en el genoma del cáncer
Graham R Bignell1, Chris D Greenman, Helen Davies
1Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Nature
|February 19, 2010
Resumen
Los investigadores identificaron miles de deleciones homocigotas en líneas celulares de cáncer, revelando conocimientos sobre la evolución del genoma del cáncer. Estos hallazgos ayudan a diferenciar entre la ruptura del ADN y las presiones de selección en el desarrollo del cáncer.
Área de la Ciencia:
- La genómica es la genómica.
- Biología del cáncer Biología del cáncer.
- Genética molecular La genética molecular.
Sus antecedentes:
- Los genomas del cáncer están moldeados por mutaciones somáticas y selección.
- Las deleciones homocigotas en el cáncer pueden dirigirse a genes de cáncer recesivo o sitios frágiles.
- Muchas deleciones homocigotas en el cáncer permanecen sin explicación.
Objetivo del estudio:
- Identificar y caracterizar las deleciones homocigotas somáticas en una gran cohorte de líneas celulares de cáncer.
- Desarrollar métodos para distinguir las causas de las deleciones homocigotas.
- Comprender los roles de la mutación y la selección en la configuración de los genomas del cáncer.
Principales métodos:
- Análisis de 2.428 deleciones homocigotas somáticas en 746 líneas de células cancerosas.
- Derivación de firmas estructurales para diferenciar las causas de supresión.
- Aplicación de firmas a grupos de eliminación inexplicables.
Principales resultados:
- Se encontró que las deleciones homocigotas afectan al 11% de los genes codificadores de proteínas, lo que indica que no son esenciales para la supervivencia celular.
- Las firmas estructurales distinguen con éxito las deleciones en sitios frágiles de las de los genes de cáncer recesivo.
- La mayoría de las deleciones inexplicables ocurrieron en regiones frágiles, con una fracción más pequeña implicando genes de cáncer recesivo.
Conclusiones:
- Las firmas estructurales son herramientas valiosas para diseccionar las mutaciones frente a las influencias de selección en los genomas del cáncer.
- Las líneas celulares de cáncer proporcionan datos ricos para la biología del cáncer y la investigación de descubrimiento de fármacos.
- Comprender las deleciones homocigotas ayuda a descifrar la evolución del genoma del cáncer e identificar posibles objetivos terapéuticos.
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