Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0677930 (
primary tumor
)
20,210
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To identify novel methylated gene promoters, we compared differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of 5-aza-2'-deoxycytidine (5-aza-dC). Out of 1776 genes that were initially 'absent (that is, silenced)' by gene expression array analysis, we selected 163 genes that were increased after 5-aza-dC treatment in at least two of three CRC cell lines. The microarray results were confirmed by Reverse Transcription-PCR, and CpG island of the gene promoters were amplified and sequenced for examination of cancer-specific methylation. Among the genes identified, the deafness, autosomal dominant 5 gene,
DFNA5
, promoter was found to be methylated in
primary tumor
tissues with high frequency (65%, 65/100). Quantitative methylation-specific PCR of
DFNA5
clearly discriminated primary CRC tissues from normal colon tissues (3%, 3/100). The mRNA expression of
DFNA5
in four of five colon cancer tissues was significantly downregulated as compared to normal tissues. Moreover, forced expression of full-length
DFNA5
in CRC cell lines markedly decreased the cell growth and colony-forming ability whereas knockdown of
DFNA5
increased cell growth in culture. Our data implicate
DFNA5
as a novel tumor suppressor gene in CRC and a valuable molecular marker for human cancer.
...
PMID:Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma. 1822 88
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.
...
PMID:Methylation of the DFNA5 increases risk of lymph node metastasis in human breast cancer. 1834 56
