DNA methylation signatures of breast cancer in peripheral T-cells

• Published in: BMC cancer Vol. 18; no. 1; p. 574
• Main Authors: Parashar, Surabhi, Cheishvili, David, Mahmood, Niaz, Arakelian, Ani, Tanvir, Imrana, Khan, Haseeb Ahmed, Kremer, Richard, Mihalcioiu, Catalin, Szyf, Moshe, Rabbani, Shafaat A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.05.2018; BioMed Central; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Blood DNA; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Care and treatment; Case-Control Studies; Development and progression; Disease Progression; DNA methylation; DNA Methylation - immunology; Epigenesis, Genetic; Epigenetic signature; Female; Healthy Volunteers; Humans; Immune system; Immunologic Surveillance - genetics; Methylation; Middle Aged; Oligonucleotide Array Sequence Analysis; Prognosis; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Blood DNA; Biomarkers; DNA methylation; Breast cancer; Epigenetic signature; Immune system
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4482-7

Immune surveillance acts as a defense mechanism in cancer, and its disruption is involved in cancer progression. DNA methylation reflects the phenotypic identity of cells and recent data suggested that DNA methylation profiles of T cells and peripheral blood mononuclear cells (PBMC) are altered in cancer progression. We enrolled 19 females with stage 1 and 2, nine with stage 3 and 4 and 9 age matched healthy women. T cells were isolated from peripheral blood and extracted DNA was subjected to Illumina 450 K DNA methylation array analysis. Raw data was analyzed by BMIQ, ChAMP and ComBat followed by validation of identified genes by pyrosequencing. Analysis of data revealed ~ 10,000 sites that correlated with breast cancer progression and established a list of 89 CG sites that were highly correlated (p < 0.01, r > 0.7, r < - 0.7) with breast cancer progression. The vast majority of these sites were hypomethylated and enriched in genes with functions in the immune system. The study points to the possibility of using DNA methylation signatures as a noninvasive method for early detection of breast cancer and its progression which need to be tested in clinical studies.