Abstract
Abstract Background: Circulating tumor cells (CTCs) are associated with prognosis in a variety of human cancers and have been proposed as a liquid biopsy for follow up examinations. We show, that established tumor suppressor and metastasis suppressor genes (CST6, BRMS1, and SOX17) are epigenetically silenced in CTCs isolated from peripheral blood of breast cancer patients. Methods: Peripheral blood was obtained from 56 patients with operable breast cancer, 27 patients with verified metastasis and 23 healthy individuals. Extraction of genomic DNA was performed in the EpCAM positive immunomagnetically selected CTC fraction of peripheral blood mononuclear cells (PBMC). DNA samples were subjected to sodium bisulphite conversion and tested for the presence of methylated and unmethylated gene promoter sequences by methylation specific PCR (MSP). All samples were also checked for CK-19 expression by RT-qPCR. Results: In CTCs of patients with operable breast cancer, CST6 promoter methylation was observed in 17.9%, BRMS1 promoter methylation in 30.4%, and SOX17 promoter methylation in 53.6%. In CTCs of patients with verified metastasis, CST6 promoter methylation was observed in 37.0%, BRMS1 promoter methylation in 44.4%, and SOX17 promoter methylation in 74.1%. Conclusions: Our results provide the first evidence that DNA methylation of tumor suppressor and metastasis suppressor genes is a hallmark feature of CTCs and confirm their heterogeneity. Our findings add a new dimension on the malignant nature of CTCs and may underlie the acquisition of malignant properties, including their stemlike phenotype. Moreover, these epigenetic markers open new possibilities for the exploitation of CTCs in monitoring cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 86. doi:10.1158/1538-7445.AM2011-86
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