Methylation of the DFNA5 increases risk of lymph node metastasis in human breast cancer

The pathogenesis of breast cancer involves multiple genetic and epigenetic events. In this study, we report an epigenetic alteration of DFNA5 in human breast cancer. DFNA5 gene was silenced in breast cancer cell lines that were methylated in the DFNA5 promoter, and restored by treatment with the dem...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-05, Vol.370 (1), p.38-43
Main Authors: Kim, Myoung Sook, Lebron, Cinthia, Nagpal, Jatin K., Chae, Young Kwang, Chang, Xiaofei, Huang, Yiping, Chuang, Tony, Yamashita, Keishi, Trink, Barry, Ratovitski, Edward A., Califano, Joseph A., Sidransky, David
Format: Article
Language:English
Subjects:
Adult
Aged
Autosomal dominant 5 gene
Biomarkers, Tumor - genetics
Breast cancer
Breast Neoplasms - pathology
Cell Line, Tumor
DFNA5
DNA Methylation
Down-Regulation
Epistasis, Genetic
Female
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
Middle Aged
Neoplasm Invasiveness
Promoter methylation
Receptors, Estrogen - antagonists & inhibitors
Receptors, Estrogen - genetics
RNA, Messenger
The human deafness
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Summary:The pathogenesis of breast cancer involves multiple genetic and epigenetic events. In this study, we report an epigenetic alteration of DFNA5 in human breast cancer. DFNA5 gene was silenced in breast cancer cell lines that were methylated in the DFNA5 promoter, and restored by treatment with the demethylating agent, 5-aza-dC, and gene knock-down of DFNA5 increased cellular invasiveness in vitro. The mRNA expression of DFNA5 in breast cancer tissues was down-regulated as compared to normal tissues. Moreover, the DFNA5 promoter was found to be methylated in primary tumor tissues with high frequency (53%, 18/34). Quantitative methylation-specific PCR of DFNA5 clearly discriminated primary breast cancer tissues from normal breast tissues (15.3%, 2/13). Moreover, methylation status of DFNA5 was correlated with lymph node metastasis in breast cancer patients. Our data implicate DFNA5 promoter methylation as a novel molecular biomarker in human breast cancer.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.03.026