Oncotarget

Research Papers:

Direct comparison study of DNA methylation markers in EpCAM-positive circulating tumour cells, corresponding circulating tumour DNA, and paired primary tumours in breast cancer

Maria Chimonidou, Areti Strati, Nikos Malamos, Sophia Kouneli, Vassilis Georgoulias and Evi Lianidou _

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Oncotarget. 2017; 8:72054-72068. https://doi.org/10.18632/oncotarget.18679

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Abstract

Maria Chimonidou1, Areti Strati1, Nikos Malamos2, Sophia Kouneli2, Vassilis Georgoulias3 and Evi Lianidou1

1Analysis of Circulating Tumour Cells Laboratory, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece

2Department of Pathology, Oncology Unit, Helena Venizelou Hospital, Athens, Greece

3Laboratory of Tumour Cell Biology, Medical School, University of Crete, Heraklion, Greece

Correspondence to:

Evi Lianidou, email: [email protected]

Keywords: liquid biopsy, circulating tumour cells, circulating tumour DNA, breast cancer, methylation specific PCR

Received: March 25, 2016     Accepted: March 29, 2017     Published: June 27, 2017

ABSTRACT

Circulating Tumour Cells (CTCs) and circulating tumour DNA (ctDNA) represent a non-invasive liquid biopsy approach for the follow-up and therapy management of cancer patients. We evaluated whether DNA methylation status in CTCs and ctDNA is comparable and whether it reflects the status of primary tumours. We compared the methylation status of three genes, SOX17, CST6 and BRMS1 in primary tumours, corresponding CTCs and ctDNA in 153 breast cancer patients and healthy individuals, by using real time methylation specific PCR. We report a clear association between the EpCAM-positive CTC-fraction and ctDNA for SOX17 promoter methylation both for patients with early (P = 0.001) and metastatic breast cancer (P = 0.046) but not for CST6 and BRMS1. In early breast cancer, SOX17 promoter methylation in the EpCAM-positive CTC-fraction was associated with CK-19 mRNA expression (P = 0.006) and worse overall survival (OS) (P = 0.044). In the metastatic setting SOX17 promoter methylation in ctDNA was highly correlated with CK-19 (P = 0.04) and worse OS (Ρ = 0.016). SOX17 methylation status in CTCs and ctDNA was comparable and was associated with CK-19 expression but was not reflecting the status of primary tumours in breast cancer. DNA methylation analysis of SOX17 in CTCs and matched ctDNA provides significant prognostic value.


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