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PMID: 19367284 Published · ppublish English Journal Article

The presence of circulating total DNA and methylated genes is associated with circulating tumour cells in blood from breast cancer patients.

British journal of cancer ·Vol. 100 ·No. 8 ·2009-04-21 ·Pages 1277-86

Van der Auwera I, Elst HJ, Van Laere SJ, Maes H, Huget P, van Dam P, Van Marck EA, Vermeulen PB, Dirix LY

Abstract

Circulating tumour cells (CTC) and tumour-related methylated DNA in blood have been separately assessed for their utility as a marker for subclinical metastasis in breast cancer. However, no studies have looked into the relation between the both molecular markers in this type of cancer. In this study, we investigated the correlations between total/methylated DNA and CTC in the blood from metastatic breast cancer patients. We simultaneously obtained whole blood, plasma and serum samples from 80 patients and 20 controls. The CellSearch System was used to enumerate CTC in blood samples. Plasma total DNA levels were determined by a QPCR method. Sera were analysed by methylation-specific QPCR for three markers: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A) and oestrogen receptor 1 (ESR1). Total DNA levels in patients were significantly increased when compared with controls (P<0.001) and correlated with the number of CTC (r=0.418, P<0.001). Hypermethylation of one or more genes was detected in 42 (53%) serum samples from breast cancer patients and in three (16%) serum samples from controls (P=0.003). APC was hypermethylated in 29%, RASSF1A in 35% and ESR1 in 20% of breast cancer cases. Detection of a methylated gene in serum was associated with the detection of CTC in blood (P=0.03). The detection of large amounts of circulating total/methylated DNA correlated with the presence of CTC in the blood from patients with breast cancer. This can be interpreted in two ways: (a) CTC are a potential source of circulating tumour-specific DNA; (b) high numbers of CTC and circulating methylated DNA are both a phenotypic feature of more aggressive tumour biology.

MeSH Terms
Adenomatous Polyposis Coli/genetics Breast Neoplasms/blood,genetics DNA/blood DNA Methylation/genetics DNA, Neoplasm/blood,genetics Estrogen Receptor alpha/genetics Female Genes, p53 Humans Polymerase Chain Reaction Receptor, ErbB-2/genetics Receptors, Estrogen/genetics Receptors, Progesterone/genetics Reference Values Tumor Suppressor Proteins/genetics
Chemicals
DNA, Neoplasm Estrogen Receptor alpha RASSF1 protein, human Receptors, Estrogen Receptors, Progesterone Tumor Suppressor Proteins DNA Receptor, ErbB-2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Van der Auwera I
Translational Cancer Research Group, Laboratory of Pathology, University of Antwerp/University Hospital Antwerp, Oncology Centre, General Hospital St-Augustinus, Wilrijk, Belgium.
Elst H J
Van Laere S J
Maes H
Huget P
van Dam P
Van Marck E A
Vermeulen P B
Dirix L Y
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
DOI
10.1038/sj.bjc.6605013
Published
2009-04-21
Pages
1277-86
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2676551
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6605013 PMC Full Text View journal details
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