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El paisaje de mutación somática del epitelio gástrico normal
Tim H H Coorens1,2, Grace Collord3,4, Hyungchul Jung3
1Wellcome Sanger Institute, Hinxton, UK. tcoorens@broadinstitute.org.
Nature
|March 20, 2025
Resumen
Las mutaciones somáticas en las glándulas gástricas se acumulan anualmente, influenciadas por procesos endógenos. Los pacientes con cáncer muestran tasas de mutación aceleradas, particularmente en las glándulas metaplásticas, con mutaciones genéticas específicas que aumentan con la edad y la inflamación.
Área de la Ciencia:
- La genómica
- Biología del cáncer
- Gastroenterología
Sus antecedentes:
- Las mutaciones somáticas en las células normales revelan procesos de envejecimiento y desarrollo precoz del cáncer.
- Comprender la evolución del epitelio gástrico es crucial para identificar los orígenes del cáncer.
Objetivo del estudio:
- Para aclarar las trayectorias de desarrollo del epitelio gástrico normal y maligno.
- Para investigar la acumulación y los impulsores de las mutaciones somáticas en el revestimiento gástrico.
Principales métodos:
- Secuenciación de todo el genoma de 238 microdisecciones de 30 individuos (18 con cáncer gástrico).
- Secuenciación dirigida de 829 microbiopsias gástricas policlonales.
Principales resultados:
- Las glándulas gástricas son monoclonales, acumulando ~ 28 variantes somáticas de un solo nucleótido por año, principalmente por procesos mutacionales endógenos.
- Las glándulas metaplásticas en pacientes con cáncer presentan cargas de mutación más altas debido a la proliferación acelerada y el daño oxidativo.
- Las trisomías recurrentes se observan en las células epiteliales gástricas, y las mutaciones somáticas en genes como ARID1A son frecuentes, aumentando con la edad y la inflamación.
Conclusiones:
- Las células epiteliales gástricas acumulan mutaciones somáticas y anomalías cromosómicas a lo largo de la vida.
- La inflamación crónica y el envejecimiento influyen significativamente en la evolución somática en el epitelio gástrico.
- Los hallazgos ofrecen información sobre los estados gástricos saludables, precancerosos y malignos, informando sobre la investigación del desarrollo del cáncer.
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