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 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.
Kim
Myoung Sook
MS
Department of Otolaryngology, Head and Neck Cancer Research Institute, Johns Hopkins University, 1550 Orleans Street 5N.03, Baltimore, MD 21231, USA.
Lebron
Cinthia
C
Nagpal
Jatin K
JK
Chae
Young Kwang
YK
Chang
Xiaofei
X
Huang
Yiping
Y
Chuang
Tony
T
Yamashita
Keishi
K
Trink
Barry
B
Ratovitski
Edward A
EA
Califano
Joseph A
JA
Sidransky
David
D
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D004843:Epistasis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics*; D000094524:Gasdermins
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins