Cell-free DNA and RNA in plasma as a new molecular marker for prostate and breast cancer
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Papadopoulou, E.
Davilas, E.
Sotiriou, V.
Georgakopoulos, E.
Georgakopoulou, S.
Koliopanos, A.
Aggelakis, F.
Dardoufas, K.
Agnanti, N. J.
Karydas, I.
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peer-reviewed
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Ann N Y Acad Sci
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In this study, we examined several molecular markers in prostate and breast cancer patients and in normal individuals. The markers tested were: variations in the quantity of plasma DNA, glutathione-S-transferase P1 gene (GSTP1), Ras association domain family 1A (RASSF1A), and ataxia telangiectasia mutated (ATM) methylation status in plasma, carcinoembryonic antigen (CEA) and prostate-specific membrane antigen (PSMA) mRNA in peripheral blood mononuclear cells (PBMC) and plasma samples from prostate cancer patients. DNA quantification in plasma was performed using real-time PCR (RT-PCR). We assessed the methylation status of GSTP1 in plasma DNA using methylation-specific PCR (MSP) assay, while the methylation status of RASSF1A and ATM genes was examined by the MethyLight technology. RT-PCR analysis was used for the detection of mRNA, PSMA, and CEA. In 58.3% of newly diagnosed prostate cancer patients and 26.7% of prostate cancer patients under therapy, plasma DNA levels were increased. Additionally, 48.5% of breast cancer patients showed plasma DNA levels above the cutoff limit. GSTP1 Promotor hypermethylation was detectable in 75% of plasma samples obtained from patients with newly diagnosed prostate cancer and in 36.8% of patients under therapy, whereas 26% and 14% of the breast cancer patients tested were positive for RASSF1A and ATM methylation, respectively. The combination of DNA load and promotor methylation status identified 88% of prostate cancer patients and 54% of breast cancer patients. This study shows that free-circulating DNA can be detected in cancer patients compared with disease-free individuals, and suggests a new, noninvasive approach for early detection of cancer.
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Antigens, Surface/blood/genetics, *Breast Neoplasms/blood/diagnosis/genetics, Carcinoembryonic Antigen/blood/genetics, Cell Cycle Proteins/blood/genetics, DNA/*blood, DNA Methylation, DNA-Binding Proteins/blood/genetics, Female, Genetic Markers, Glutamate Carboxypeptidase II/blood/genetics, Glutathione S-Transferase pi/blood/genetics, Humans, Male, Plasma/*chemistry, Promoter Regions, Genetic, *Prostatic Neoplasms/blood/diagnosis/genetics, Protein-Serine-Threonine Kinases/blood/genetics, RNA/*blood, *Tumor Markers, Biological, Tumor Suppressor Proteins/blood/genetics
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http://www.ncbi.nlm.nih.gov/pubmed/17108217
http://onlinelibrary.wiley.com/store/10.1196/annals.1368.032/asset/annals.1368.032.pdf?v=1&t=h1sz13hz&s=6096b5bb41fe7a85a2e431061e077ad6968197f7
http://onlinelibrary.wiley.com/store/10.1196/annals.1368.032/asset/annals.1368.032.pdf?v=1&t=h1sz13hz&s=6096b5bb41fe7a85a2e431061e077ad6968197f7
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en
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής