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

Myoung Sook Kim, Cinthia Lebron, Jatin K. Nagpal, Young Kwang Chae, Xiaofei Chang, Yiping Huang, Tony Chuang, Keishi Yamashita, Barry Trink, Edward A. Ratovitski, Joseph A. Califano, David Sidransky

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)38-43
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number1
DOIs
StatePublished - May 23 2008

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Keywords

  • Autosomal dominant 5 gene
  • Breast cancer
  • DFNA5
  • Promoter methylation
  • The human deafness

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, M. S., Lebron, C., Nagpal, J. K., Chae, Y. K., Chang, X., Huang, Y., Chuang, T., Yamashita, K., Trink, B., Ratovitski, E. A., Califano, J. A., & Sidransky, D. (2008). Methylation of the DFNA5 increases risk of lymph node metastasis in human breast cancer. Biochemical and Biophysical Research Communications, 370(1), 38-43. https://doi.org/10.1016/j.bbrc.2008.03.026