Study of DOK4 gene expression and promoter methylation in sporadic breast cancer

Azar Heidarizadi,  Mahdieh Salimi, Hossein Mozdarani

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.