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La coevolución del genoma y el epigenoma en el cáncer colorrectal
Timon Heide1,2, Jacob Househam1,3, George D Cresswell1
1Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
Nature
|October 26, 2022
Resumen
Este estudio mapea el cáncer colorrectal
Área de la Ciencia:
- La genómica
- La epigenética
- Biología del cáncer
Sus antecedentes:
- Las neoplasias colorrectales son una causa importante de mortalidad por cáncer.
- Los estudios genómicos por sí solos no explican completamente el desarrollo del cáncer.
- Comprender la interacción entre el genoma y el epigenoma es crucial.
Objetivo del estudio:
- Investigar la coevolución del genoma y el epigenoma en los tumores colorrectales.
- Para analizar la heterogeneidad genética y epigenética en la resolución de un solo clon.
- Explorar el papel de las alteraciones epigenéticas en la tumorigénesis colorrectal.
Principales métodos:
- Perfiles multi-ómicos espaciales de las glándulas colorrectales individuales.
- Se recogieron 1.370 muestras de 30 cánceres primarios y 8 adenomas.
- Generación de datos de accesibilidad de la cromatina, de todo el genoma y de todo el transcriptoma.
Principales resultados:
- Se identificó una selección positiva para mutaciones en el ADN en genes modificadores de la cromatina.
- Se descubrieron alteraciones recurrentes de la accesibilidad de la cromatina somática, incluso en regiones reguladoras de factores cancerígenos.
- Cambios observados en todo el genoma en la accesibilidad de unión al factor de transcripción (CTCF, SOX, HOX) y en la señalización del interferón.
- Se ha demostrado la heredabilidad de las alteraciones de accesibilidad a la cromatina, distinguiendo los adenomas de los cánceres.
- Se demostró que el epigenoma influye en la acumulación de mutaciones en el ADN.
Conclusiones:
- Proporciona un mapa completo de la heterogeneidad genética y epigenética en el cáncer colorrectal.
- Destaca la participación de los genes del desarrollo en el desarrollo del tumor.
- Sugiere una relación bidireccional entre el epigenoma y el genoma en la progresión del cáncer.
- Ofrece información fundamental sobre la biología del cáncer colorrectal.
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