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La historia evolutiva de 2.658 tipos de cáncer
Moritz Gerstung1,2,3, Clemency Jolly4, Ignaty Leshchiner5
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK. moritz.gerstung@ebi.ac.uk.
Nature
|February 7, 2020
Resumen
El cáncer evoluciona a través de cambios genómicos con el tiempo. Este estudio analizó 2.658 cánceres, revelando cómo las mutaciones y las alteraciones del número de copias dan forma al desarrollo del tumor, ofreciendo información para la detección temprana del cáncer.
Área de la Ciencia:
- La genómica
- Biología del cáncer
- La medicina evolutiva
Sus antecedentes:
- El cáncer surge de la evolución somática, con aberraciones genómicas y procesos mutacionales que impulsan el desarrollo del tumor.
- El análisis de los genomas del cáncer proporciona información sobre el momento de estos eventos y su historia evolutiva.
Objetivo del estudio:
- Para reconstruir la historia evolutiva de los procesos mutacionales y las mutaciones del conductor en 38 tipos de cáncer.
- Comprender la secuencia temporal de las alteraciones genómicas durante la oncogénesis.
Principales métodos:
- Secuenciación de todo el genoma de 2.658 muestras de cáncer a través del Consorcio de Análisis Pan-Cancer de Genomas Totales (PCAWG).
- Análisis de los datos del Consorcio Internacional del Genoma del Cáncer (ICGC) y el Atlas del Genoma del Cáncer (TCGA).
- Reconstrucción computacional de las trayectorias evolutivas del cáncer.
Principales resultados:
- La oncogénesis temprana implica mutaciones genéticas específicas y ganancias de número de copias (por ejemplo, trisomía 7 en glioblastoma).
- Los cambios de espectro mutacional ocurren en el 40% de los tumores durante la evolución, con etapas posteriores que muestran diversificación de genes impulsores e inestabilidad genómica.
- Las mutaciones del conductor a menudo preceden el diagnóstico de cáncer por muchos años o décadas.
Conclusiones:
- La evolución del cáncer se caracteriza por trayectorias distintas influenciadas por eventos genómicos en etapa temprana y tardía.
- Comprender estos patrones evolutivos puede identificar oportunidades para la detección temprana del cáncer.
- El estudio proporciona una línea de tiempo completa del desarrollo del cáncer desde una perspectiva genómica.
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