Epigenetic silencing of novel tumor suppressors in malignant melanoma.
Cancer Res
; 66(23): 11187-93, 2006 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-17145863
ABSTRACT
Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified 17 genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine. Eight of these genes have not been previously shown to undergo DNA methylation in any form of cancer. Three of the genes, QPCT, CYP1B1, and LXN, are densely methylated in >95% of uncultured melanoma tumor samples. Reexpression of either of two of the silenced genes, HOXB13 and SYK, resulted in reduced colony formation in vitro and diminished tumor formation in vivo, indicating that these genes function as tumor suppressors in melanoma.
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Base de dados:
MEDLINE
Assunto principal:
Inativação Gênica
/
Proteínas Supressoras de Tumor
/
Epigênese Genética
/
Melanoma
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article