Evaluation of Methylation Status in the 5'UTR Promoter Region of the DBC2 Gene as a Biomarker in Sporadic Breast Cancer

Document Type : Research Article

Authors

1 . Department of Cell Research Center and Medical Genetics, Sarem Women`s Hospital, Tehran, Iran ;. Department of Biology, Science Faculty, Razi University, Kermanshah, Iran

2 . Department of Cell Research Center and Medical Genetics, Sarem Women`s Hospital, Tehran, Iran ;. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

3 4. Department of Surgery, Atiyeh Hospital, Tehran, Iran

4 . Department of Cell Research Center and Medical Genetics, Sarem Women`s Hospital, Tehran, Iran ;5. GRC, University of Social Welfare Sciences and Rehabilitation, Tehran, Iran

5 . Department of Cell Research Center and Medical Genetics, Sarem Women`s Hospital, Tehran, Iran

6 . Department of Biology, Science Faculty, Razi University, Kermanshah, Iran

Abstract

Objective
Breast cancer is one of the most common malignancies in women worldwide. It is caused by a number of genetic and epigenetic factors. Aberrant hypermethylation of the promoter regions in specific genes is a key event in the formation and progression of breast cancers as well as the DBC2 gene, as a tumor suppressor gene. Different studies show that the DBC2 gene is inactivated through epigenetic mechanisms such as methylation in its promoter region. In this study, authors have tried to analyze methylation status in the promoter region of DBC2 gene in affected women and healthy controls. Materials and Methods: In this experimental study, we evaluated the methylation status of DBC2 gene with nested methylation-specific PCR (MSPCR) using specific methylated and unmethylated primer sets, in three separate PCR reactions. We used 50 tissue and blood samples of patients with breast cancer, 5 normal tissues and also 30 normal blood samples. Results were evaluated by the Mann-Whitney test, SPSS 16.0 statistical software. Results: Nested MSPCR results demonstrated that the frequency of the DBC2 promoter region methylation status in tumor and blood samples of the affected patients was significantly higher than that of the corresponding normal controls. Conclusion: DBC2 gene inactivation by methylation of CpG islands in the promoter region probably is a crucial step in the process of cell proliferation and susceptibility to different cancers, including breast cancer. Our study provides new evidence that aberrant methylation of the DBC2 gene is involved in the tumorigenesis of breast cancer. DNA methylation in this gene is proven to be a potential marker for tumor diagnosis and prognosis, as well as a novel therapeutic target.

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