J Breast Cancer.  2017 Mar;20(1):12-19. 10.4048/jbc.2017.20.1.12.

Detection of Methylated Circulating DNA as Noninvasive Biomarkers for Breast Cancer Diagnosis

• Cheuk IW
• Shin VY
• Kwong A

• KMID: 2379394
• DOI: http://doi.org/10.4048/jbc.2017.20.1.12

Abstract

Internationally, breast cancer is the most common female cancer, and is induced by a combination of environmental, genetic, and epigenetic risk factors. Despite the advancement of imaging techniques, invasive sampling of breast epithelial cells is the only definitive diagnostic procedure for patients with breast cancer. To date, molecular biomarkers with high sensitivity and specificity for the screening and early detection of breast cancer are lacking. Recent evidence suggests that the detection of methylated circulating cell-free DNA in the peripheral blood of patients with cancer may be a promising quantitative and noninvasive method for cancer diagnosis. Methylation detection based on a multi-gene panel, rather than on the methylation status of a single gene, may be used to increase the sensitivity and specificity of breast cancer screening. In this review, the results of 14 relevant studies, investigating the efficacy of cell-free DNA methylation screening for breast cancer diagnosis, have been summarized. The genetic risk factors for breast cancer, the methods used for breast cancer detection, and the techniques and limitations related to the detection of cell-free DNA methylation status, have also been reviewed and discussed. From this review, we conclude that the analysis of peripheral blood or other samples to detect differentially methylated cell-free DNA is a promising technique for use in clinical settings, and may improve the sensitivity of screening for both, early detection and disease relapse, and thus improve the future prognosis of patients with breast cancer.

Keyword

Breast neoplasms; Complementary DNA; Early detection of cancer

MeSH Terms

Biomarkers*
Breast Neoplasms*
Breast*
Diagnosis*
DNA Methylation
DNA*
DNA, Complementary
Early Detection of Cancer
Epigenomics
Epithelial Cells
Female
Humans
Mass Screening
Methods
Methylation
Prognosis
Recurrence
Risk Factors
Sensitivity and Specificity
Biomarkers
DNA
DNA, Complementary

Figure

• 

  Figure 1 Hypomethylation and hypermethylation of human genome. (A) In normal cells, cytosine and guanine dinucleotides (CpG) islands in the promoter region are unmethylated. (B) In cancer cells, promoter hypomethylation of oncogenic genes lead to transcription initiation. (C) Promoter hypermethylation of tumor suppressor genes lead to gene silencing. (D) Global hypomethylation affects gene integrity and stability.

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