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ASSESSMENT OF THE VALUE OF METHYLATION FEATURES IN DIFFERENT TISSUES FOR PREOPERATIVE IDENTIFICATION OF HIGH-RISK
K Kankava1, E Kvaratskhelia1, G Burkadze2
1Tbilisi State Medical University; 1Department of Molecular and Medical Genetics; Georgia.
Abstract:
Epigenetic changes in breast cancer patients have long been believed to be a promising marker for clinical management - early detection, prognostication, etc. Various approaches are available to test global DNA or target gene methylation status. We used some of them in different tissues of patients with breast cancer to analyze possible links between epigenetic parameters and their value for predicting clinicopathological characteristics (most importantly stage and lymph node status) of tumors. Patients with ductal and lobular invasive carcinoma were included in the study along with age-matched controls. Blood, tumor tissue and normal breast ductal epithelial cells were investigated using MS-HRM technique (for BRCA1 gene promoter methylation assessment), COBRA-PCR (for Alu element methylation quantification) and ELISA-based method (for global DNA methylation estimation). These parameters were analyzed in comparison to clinical, histologic and phenotypic characteristics of the tumors. BRCA1 promoter methylation was detected exclusively in tumor tissues and in only two cases, both of which had aggressive phenotype. Alu and global DNA methylation showed markedly low levels in all tissues of cancer patients compared to healthy controls, with extreme hypomethylation in tumor tissue. Changes in these two parameters were not always concordant. Methylation levels detected in blood showed rather weak relationship with clinicopathological characteristics of tumors. We could conclude that tested parameters are not useful for preoperative determination of tumor stage or lymph node status, neither any other clinicopathological characteristics of tumors. Epigenetics signatures of different tissues of the same patient are not homogenous. Given the uniform picture of DNA methylation in blood in some of investigated groups, additional data and very careful approach are required when considering using it as a diagnostic or predictive tool.
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