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Updated: Dec 22, 2025
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Study of DOK4 gene expression and promoter methylation in sporadic breast cancer
A Heidarizadi1, M Salimi2, H Mozdarani3
1Department of Molecular Genetics, Faculty of Basic Sciences, Islamic Azad University, Shiraz, Iran.
Abstract:
The analysis of DNA methylation patterns in circulating cell-free DNA in body fluids is an analyte of great interest in clinical research. Downstream of Kinase (DOK) proteins represent a multigenic family of adaptors that includes negative regulators of immune cell signaling and plays important roles in signaling, cellular growth, and survival. The aim of the present study was to investigate the pattern of promoter methylation and expression of the DOK4 gene in breast cancer, and its possible association with histoclinical characteristics. The mRNA expression of the DOK4 gene was evaluated in 164 breast tissues using Real-Time RT-PCR. The promoter methylation of this gene was evaluated in breast tissues and plasma free nucleic acids by MS-PCR. The associations of gene expression and DNA methylation with histoclinical characteristics of the patients were studied. The data indicated that DOK4 mRNA expression was significantly downregulated in breast tumors compared with normal control in all the stages. About 40% of breast tumors showed DOK4 promoter methylation, which somehow confirms the DOK4 promoter methylation rate in the plasma. The data revealed that the reduction in DOK4 expression in all breast cancer groups could well endorse this gene as a candidate possible marker for future investigations on breast cancer management. The DOK4 methylation pattern in breast tissue was correlated with plasma free nucleic acids but the state of DOK4 promoter methylation alone may not be sufficient to differentiate between the two cancerous and normal groups.
Insights
Downstream of Kinase 4 (DOK4) gene expression is reduced in breast tumors, with promoter methylation observed in nearly half of cases. This suggests DOK4 may be a potential biomarker for breast cancer management.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA methylation analysis in cell-free DNA is crucial for clinical research.
- Downstream of Kinase (DOK) proteins are involved in cell signaling, growth, and survival.
- DOK4, a member of the DOK protein family, plays a role in cellular processes.
Purpose of the Study:
- To investigate the promoter methylation and expression patterns of the DOK4 gene in breast cancer.
- To explore the association between DOK4 methylation/expression and histoclinical characteristics.
- To assess DOK4 as a potential biomarker for breast cancer.
Main Methods:
- Real-Time RT-PCR was used to evaluate DOK4 mRNA expression in 164 breast tissues.
- Methylation-Specific PCR (MS-PCR) assessed DOK4 promoter methylation in breast tissues and plasma.
- Statistical analyses examined correlations between gene expression, DNA methylation, and patient histoclinical data.
Main Results:
- DOK4 mRNA expression was significantly downregulated in breast tumors across all stages compared to normal controls.
- Approximately 40% of breast tumors exhibited DOK4 promoter methylation, consistent with plasma findings.
- DOK4 methylation in breast tissue correlated with plasma free nucleic acid methylation, but methylation alone did not reliably distinguish between cancerous and normal groups.
Conclusions:
- Reduced DOK4 expression in breast cancer suggests its potential as a biomarker.
- DOK4 promoter methylation patterns in tissue and plasma are linked.
- Further investigation is warranted to establish DOK4's role in breast cancer management.
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