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Los tumores de ratón cromosómicamente inestables tienen alteraciones genómicas similares a los diversos cánceres
Richard S Maser1, Bhudipa Choudhury, Peter J Campbell
1Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|May 23, 2007
Resumen
Los modelos de ratones genéticamente inestables ayudan al descubrimiento de genes de cáncer. Estos modelos identificaron eventos genéticos comunes, como las deleciones de FBXW7 y PTEN, en los linfomas de ratón y en la leucemia linfoblástica aguda/linfoma de células T humanas (T-ALL), destacando las similitudes entre especies de cáncer.
Área de la Ciencia:
- Oncología Oncología.
- La genómica es la genómica.
- Oncología Comparada y Oncología Comparada.
Sus antecedentes:
- Los genomas del cáncer son complejos, por lo que es difícil identificar los principales impulsores genéticos de la transformación neoplásica.
- Los modelos de ratón son cruciales para comprender el desarrollo del cáncer y descubrir nuevos objetivos terapéuticos.
Objetivo del estudio:
- Evaluar la utilidad de modelos de ratón diseñados y cromosómicamente inestables para el descubrimiento de genes de cáncer.
- Determinar el grado de superposición en las aberraciones del número de copias asociadas al cáncer entre los modelos de ratón y los cánceres humanos.
Principales métodos:
- Ratones diseñados propensos al linfoma con inestabilidad cromosómica.
- Análisis oncogenómico comparativo incluyendo re-secuenciación dirigida.
- Identificación de las aberraciones del número de copia (CNA) y su localización sintética.
Principales resultados:
- Se encontró que FBXW7 y PTEN se eliminan comúnmente tanto en los linfomas murinos como en la leucemia linfoblástica aguda / linfoma (T-ALL) de células T humanas.
- Los cánceres de murino exhibieron amplificaciones y deleciones recurrentes en los loci sinténicos a los de la T-ALL humana y otros tipos de tumores humanos.
- Los eventos genómicos en tumores de ratón y humanos muestran una alta concordancia, lo que sugiere procesos biológicos compartidos impulsados por eventos genéticos ortólogos.
Conclusiones:
- Los modelos de cáncer de ratón genómicamente inestables son herramientas valiosas para descubrir los eventos impulsores biológicos en los cánceres humanos.
- La superposición de las alteraciones genómicas entre los tumores de ratón y humanos apoya el uso de estos modelos para la investigación traslacional del cáncer.
- La oncogenómica comparativa revela mecanismos genéticos conservados que subyacen al desarrollo del cáncer en todas las especies.
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