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Inducción de tumores en ratones por hipometilación genómica

François Gaudet¹, J Graeme Hodgson, Amir Eden

¹Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Science (New York, N.Y.)

|April 19, 2003

Resumen

La hipometilación del ADN, un cambio epigenético, juega un papel causal en el desarrollo del cáncer. La reducción de la ADN metiltransferasa 1 (Dnmt1) en ratones condujo a la hipometilación de todo el genoma y a linfomas agresivos de células T.

Área de la Ciencia:

La epigenética es la epigenética.
Biología del cáncer Biología del cáncer.
Genética La genética.

Sus antecedentes:

La hipometilación del ADN en todo el genoma se observa en los cánceres humanos.
Su papel como causa o consecuencia de la tumorigénesis sigue sin estar claro.

Objetivo del estudio:

Para investigar el papel causal de la hipometilación del ADN en la formación de tumores.
Para explorar el vínculo entre la hipometilación y la inestabilidad cromosómica.

Principales métodos:

Ratones generados con un alelo hipomórfico de ADN metiltransferasa 1 (Dnmt1).
Reducción de la expresión de Dnmt1 al 10% de los niveles de tipo silvestre, causando hipometilación en todo el genoma.

Principales resultados:

Los ratones mutantes exhibieron ronchas al nacer.
Desarrolló linfomas agresivos de células T a los 4-8 meses de edad.
Los linfomas mostraron una alta frecuencia de trisomía del cromosoma 15.

Conclusiones:

La hipometilación del ADN juega un papel causal en el desarrollo del cáncer.
La hipometilación puede promover la formación de tumores al inducir la inestabilidad cromosómica.

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