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Updated: Dec 26, 2025

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Published on: January 12, 2020

Las mutaciones conductoras raras en los carcinomas de células escamosas de cabeza y cuello convergen en la

Sampath K Loganathan¹, Krista Schleicher^1,2, Ahmad Malik^1,2

¹Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Science (New York, N.Y.)

|March 14, 2020

Resumen

Los investigadores identificaron 15 genes supresores de tumores, incluidos ADAM10 y AJUBA, que suprimen el carcinoma de células escamosas de la cabeza y el cuello (HNSCC). Estos genes promueven la señalización del receptor NOTCH, y su inactivación es un sello distintivo de HNSCC.

Área de la Ciencia:

En el campo de la oncología
La genética
Biología molecular

Sus antecedentes:

La mayoría de los cánceres humanos exhiben algunas mutaciones de alta frecuencia y muchas mutaciones de "cola larga" de baja frecuencia con roles funcionales desconocidos.
La importancia de las alteraciones genéticas de baja frecuencia en el desarrollo del cáncer sigue siendo en gran medida inexplorada.

Objetivo del estudio:

Investigar las consecuencias funcionales de las mutaciones de "cola larga" en el carcinoma de células escamosas de la cabeza y el cuello (HNSCC).
Para identificar los genes que, cuando mutan, impulsan el desarrollo del tumor en HNSCC.

Principales métodos:

Se utilizó el cribado in vivo de CRISPR en ratones para evaluar el impacto de las mutaciones en 484 genes de "cola larga" en HNSCC.
Mutaciones genéticas analizadas, pérdida monoalélica y su asociación con la señalización y mutaciones del receptor NOTCH en muestras humanas de HNSCC.

Principales resultados:

Identificaron 15 genes supresores de tumores que suprimen el desarrollo de HNSCC en ratones.
Se descubrió que ADAM10 y AJUBA actúan como supresores de tumores haploinsufficientes al mejorar la señalización de los receptores NOTCH.
Se encontró que las mutaciones ADAM10 y AJUBA o la pérdida monoalélica ocurren en el 28% de los casos de HNSCC y se excluyen mutuamente con las mutaciones del receptor NOTCH.

Conclusiones:

La inactivación de la vía de señalización NOTCH es un evento clave en el 67% de los casos de HNSCC en humanos.
ADAM10 y AJUBA son supresores tumorales críticos en HNSCC, destacando la importancia de la vía NOTCH en este tipo de cáncer.

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