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El repertorio de firmas mutacionales en el cáncer humano

Ludmil B Alexandrov¹, Jaegil Kim², Nicholas J Haradhvala^2,3

¹Department of Cellular and Molecular Medicine, Department of Bioengineering, Moores Cancer Center, University of California, San Diego, CA, USA.

|February 7, 2020

Resumen

Los genomas del cáncer acumulan mutaciones de varios procesos, cada uno de los cuales deja una firma única. Este estudio identificó 81 firmas mutacionales distintas en miles de genomas de cáncer, revelando vínculos con exposiciones y defectos de reparación de ADN.

Área de la Ciencia:

La genómica
Biología del cáncer
Las firmas mutacionales

Sus antecedentes:

Las mutaciones somáticas en el cáncer surgen de procesos mutacionales distintos.
Cada proceso genera una firma mutacional característica.
Comprender estas firmas es crucial para la investigación del cáncer.

Objetivo del estudio:

Para caracterizar las firmas mutacionales en un gran conjunto de datos de genomas de cáncer humano.
Identificar nuevas firmas y perfeccionar las existentes.
Para asociar las firmas con exposiciones y procesos de mantenimiento del ADN.

Principales métodos:

Análisis de 84,729,690 mutaciones somáticas de 4,645 secuencias de genoma completo y 19,184 de exoma.
Se utilizaron datos del Consorcio de Análisis Pancancerígeno de Genomas Totales (PCAWG).
Se han identificado firmas de una sola base, base doble, base agrupada e indel.

Principales resultados:

Se descubrieron 49 sustituciones de una sola base, 11 sustituciones de base doble, 4 sustituciones de base agrupada y 17 pequeñas firmas de inserción y eliminación.
El gran conjunto de datos permitió la separación de firmas superpuestas y la descomposición en mecanismos subyacentes.
Firmas asociadas con exposiciones exógenas/endógenas y mantenimiento defectuoso del ADN.

Conclusiones:

Este análisis exhaustivo proporciona una visión sistemática de los procesos mutacionales en el cáncer humano.
Identificó numerosas firmas mutacionales, algunas con causas desconocidas.
Los hallazgos contribuyen a comprender el desarrollo del cáncer y los posibles objetivos terapéuticos.

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