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Mutaciones inactivadoras de los genes de la acetiltransferasa en el linfoma de células B

Laura Pasqualucci¹, David Dominguez-Sola, Annalisa Chiarenza

¹Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA. lp171@columbia.edu

|March 11, 2011

Resumen

Las mutaciones en los genes CREBBP y EP300, que regulan la actividad génica, son comunes en el linfoma folicular y el linfoma difuso de células B grandes. Estas alteraciones en las histona acetiltransferasas (HAT) contribuyen al desarrollo del linfoma.

Área de la Ciencia:

Oncología Oncología.
Biología Molecular Biología Molecular
Genética La genética.

Sus antecedentes:

Los linfomas de células B no Hodgkin (LNH) son diversos tipos de cáncer impulsados por mutaciones genéticas.
Las lesiones genéticas clave involucran oncogenes y genes supresores de tumores.

Objetivo del estudio:

Investigar el papel de los genes CREBBP y EP300 en la patogénesis del linfoma folicular (FL) y el linfoma difuso de células B grandes (DLBCL).
Para identificar los mecanismos genéticos compartidos en los subtipos de células B comunes del NHL.

Principales métodos:

Análisis de las deleciones genómicas y mutaciones somáticas en los genes CREBBP y EP300 en muestras de pacientes con FL y DLBCL.
Evaluación del impacto funcional de estas mutaciones en la actividad de la histona acetiltransferasa (HAT).
Evaluación de la regulación mediada por acetilación de la oncoproteína BCL6 y el supresor de tumores p53.

Principales resultados:

Aproximadamente el 39% de los casos de DLBCL y el 41% de los casos de FL presentan mutaciones o deleciones inactivantes en CREBBP o EP300.
Estas alteraciones genéticas afectan típicamente a un alelo, lo que sugiere que la dosis reducida de HAT es crítica.
Las mutaciones conducen a una inactivación deteriorada de la oncoproteína BCL6 y una activación reducida del supresor tumoral p53.

Conclusiones:

Las mutaciones CREBBP/EP300 representan un mecanismo patogenético significativo en las células B comunes del NHL.
Estos hallazgos resaltan la importancia de la actividad de HAT en la linfomagénesis.
Los resultados sugieren posibles estrategias terapéuticas dirigidas a las vías de acetilación / desacetilación.

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