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El panorama de la mutación somática en las células epiteliales colorrectales normales
Henry Lee-Six1, Sigurgeir Olafsson1, Peter Ellis1
1Wellcome Sanger Institute, Hinxton, UK.
Nature
|October 25, 2019
Resumen
Los cambios neoplásicos colorrectales tempranos ocurren en el tejido morfológicamente normal. La secuenciación de todo el genoma revela probables mutaciones en el 1% de las criptas colorrectales normales, lo que indica que el cáncer se desarrolla a partir de cambios generalizados.
Área de la Ciencia:
- La genómica
- Biología del cáncer
- Patología molecular
Sus antecedentes:
- La secuencia adenoma-carcinoma colorrectal es un modelo conocido para el desarrollo del cáncer.
- Los cambios neoplásicos tempranos en el tejido colorrectal morfológicamente normal son poco conocidos.
- La mayoría de los tipos de cáncer tienen un entendimiento limitado de sus primeras fases.
Objetivo del estudio:
- Investigar los primeros cambios genéticos en el desarrollo de neoplasias colorrectales.
- Para analizar las alteraciones genéticas somáticas en criptas colorrectales morfológicamente normales.
- Comprender la prevalencia y la naturaleza de las mutaciones conductoras tempranas en el epitelio colorrectal.
Principales métodos:
- Secuenciación de todo el genoma de cientos de criptas colorrectales normales de 42 personas.
- Análisis de las firmas mutacionales y las mutaciones conductoras en el tejido colorrectal normal.
- Evaluación cuantitativa de la evolución genómica y clonal en el epitelio colorrectal.
Principales resultados:
- Firmas identificadas de procesos mutacionales ubicuos, continuos e intermitentes.
- Se encontraron mutaciones conductor probables en aproximadamente el 1% de las criptas colorrectales normales en individuos de mediana edad.
- Se demostró que los cánceres colorrectales tienen cargas mutacionales significativamente más altas que las células normales.
Conclusiones:
- Los adenomas y carcinomas colorrectales surgen de un proceso neoplásico generalizado en el epitelio morfológicamente normal.
- Las alteraciones genéticas en etapa temprana son comunes en las criptas colorrectales normales.
- La secuenciación de células colorrectales normales proporciona información cuantitativa crucial sobre la evolución genómica y clonal del cáncer.
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