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Plasticidad fenotípica y control genético en la evolución del cáncer colorrectal
Jacob Househam1,2, Timon Heide1,3, George D Cresswell1
1Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
Nature
|October 26, 2022
Resumen
La mayoría de los cambios genéticos en el cáncer colorrectal (CRC) no afectan la expresión génica o la evolución del tumor. En cambio, la plasticidad transcripcional, o la capacidad de los genes para cambiar su actividad, está muy extendida dentro de los tumores.
Área de la Ciencia:
- En el campo de la oncología
- La genómica
- Biología molecular
Sus antecedentes:
- La heterogeneidad intratumoral surge de la variación genética y epigenética y de la plasticidad transcripcional.
- Las contribuciones específicas de estos procesos a la evolución tumoral no se comprenden completamente.
Objetivo del estudio:
- Investigar la interacción entre la ascendencia genética, la expresión génica y la evolución subclonal en el cáncer colorrectal (CRC).
- Determinar en qué medida la variación genética intratumoral influye en los rasgos fenotípicos y la progresión tumoral.
Principales métodos:
- Secuenciación del genoma completo y del transcriptoma emparejado de muestras de cáncer colorrectal (CRC) con resolución espacial.
- Análisis de los loci de rasgos cuantitativos de expresión somática (eQTL) para identificar los controles genéticos de la expresión génica.
- Inferencia computacional de filogenias tumorales para analizar el patrón espacial y la selección subclonal.
Principales resultados:
- La ascendencia genética intratumoral afecta con poca frecuencia la expresión génica y la evolución subclonal en el CCR.
- La mayoría de las variaciones de expresión génica intratumoral son plásticas, no hereditarias.
- La mayoría de las variaciones genéticas dentro de los tumores CRC tienen consecuencias fenotípicas limitadas, mientras que la plasticidad transcripcional es prevalente.
Conclusiones:
- La plasticidad transcripcional juega un papel más importante que la variación genética en la configuración del fenotipo de los tumores de cáncer colorrectal (CRC).
- Comprender estas dinámicas es crucial para desarrollar terapias dirigidas y predecir la respuesta al tratamiento en la CCR.
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