Epigenetic silencing of novel tumor suppressors in malignant melanoma

被引:140
作者
Muthusamy, Viswanathan
Duraisamy, Sekhar
Bradbury, C. Matthew
Hobbs, Cara
Curley, David P.
Nelson, Betsy
Bosenberg, Marcus
机构
[1] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA
[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
关键词
D O I
10.1158/0008-5472.CAN-06-1274
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:11187 / 11193
页数:7
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