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Transcriptional silencing of the Dickkopfs-3 (Dkk-3) gene by CpG hypermethylation in acute lymphoblastic leukaemia
Autor(es) : Roman-Gomez, J. (José)
Jimenez-Velasco, A. (A.)
Aguirre, X. (Xavier)
Castillejo, J.A. (J.A.)
Navarro, G. (Germán)
Barrios, M. (M.)
Andreu, E.J. (Enrique José)
Prosper, F. (Felipe)
Heiniger, A. (A.)
Torres, A. (Antonio)
Palabras clave : Acute lymphoblastic leukaemia
CpG island
Fecha incorporación: 2004
Editorial : H K Lewis and Co, Ltd.
Versión del editor: http://www.nature.com/bjc/journal/v91/n4/full/6602008a.html
ISSN: 0007-0920
Cita: Román-Gómez, J., Jiménez-Velasco, A., Agirre, X., Castillejo, J. A., Navarro, G., Barrios, M. et al. Transcriptional silencing of the Dickkopfs-3 (Dkk-3) gene by CpG hypermethylation in acute lymphoblastic leukaemia. Br. J. Cancer 2004; 91: 707 – 713
Dkk-3 is a newly characterised mortalisation-related gene and an antagonist of the Wnt oncogenic signalling pathway whose expression is decreased in a variety of cancer cell lines, suggesting that the Dkk-3 gene, located at chromosome 11p15.1, functions as a tumour suppressor gene. Although 11p15 is a ‘hot spot’ for methylation in acute lymphoblastic leukaemia (ALL), the role of Dkk-3 abnormalities has never been evaluated in this disease. We analysed CpG island methylation of the Dkk-3 promoter in six ALL cell lines and 183 ALL patients. We observed Dkk-3 hypermethylation in all cell lines and in cells from 33% (60/183) of ALL patients. Moreover, Dkk-3 methylation was associated with decreased Dkk-3 mRNA expression and this expression was restored after exposure to the demethylating agent 5-AzaC. Clinical features did not differ between hypermethylated and unmethylated patients. Estimated disease-free survival (DFS) and overall survival at 10 and 11 years, respectively, were 49.8 and 45.6% for normal patients and 10.5 and 15.1% for hypermethylated patients (P¼0.001 and 0.09). Multivariate analysis demonstrated that Dkk-3 methylation was an independent prognostic factor predicting DFS (P¼0.0009). Our data suggest that Dkk-3 methylation occurs at an early stage in ALL pathogenesis and probably influences the clinical behaviour of the disease.
Enlace permanente: http://hdl.handle.net/10171/17238
Aparece en las colecciones: DA - CIMA - Oncología - Síndromes mieloproliferativos - Artículos de Revista
DA - CIMA - Oncología - Terapia celular - Artículos de Revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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Fichero:  2004_BJC_Roman-Gomez_Transcriptional silencing of the Dickkopfs-3 gene by CpG hypermethylation in acute lymphoblastic leukaemia.pdf
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