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

doi:10.1016/j.bbrc.2008.03.026

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^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

92 Scopus citations

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 language	English (US)
Pages (from-to)	38-43
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	370
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2008.03.026
State	Published - May 23 2008

Keywords

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

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2008.03.026

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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

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title = "Methylation of the DFNA5 increases risk of lymph node metastasis in human breast cancer",

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.",

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

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AU - Chang, Xiaofei

AU - Huang, Yiping

AU - Chuang, Tony

AU - Yamashita, Keishi

AU - Trink, Barry

AU - Ratovitski, Edward A.

AU - Califano, Joseph A.

AU - Sidransky, David

PY - 2008/5/23

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N2 - 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.

AB - 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.

KW - Autosomal dominant 5 gene

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KW - Promoter methylation

KW - The human deafness

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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