Neoplastic Characteristics of the DNA Found in the Plasma of Cancer Patients

Département de Physiologie végétale, Faculté des Sciences, Université de Genève, Suisse.
Oncology (Impact Factor: 2.42). 02/1989; 46(5):318-22. DOI: 10.1159/000226740
Source: PubMed


About one third of patients with various malignant diseases were found to have extractable amounts of DNA in their plasma whereas no DNA could be detected in normal controls. Using the test established by one of us (M.B.), which is based on decreased strand stability of cancer cell DNA, we have found that several plasma DNA originate from cancer cells.

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    • "Mainly in solid tumors (e.g. lung, colon, breast and prostate) which constitute 90% of all cancers in Europe, increased levels of cell-free DNA have been found to be discriminatory between patients and healthy individuals or patients with nonmalignant diseases [10]. In prostate cancer, several studies demonstrated the presence of tumor characteristic genetic (i.e. "
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    ABSTRACT: Urinary DNA is increasingly gaining importance in diagnosis of urological malignancies. Especially cell-free DNA originating from apoptotic and necrotic cells of the early tumor could become a key target for early stage tumor diagnosis. Aberrant DNA methylation forms tumor cell characteristic epigenetic profiles which are covalently established before any tumor related aberration at transcriptional or protein level has occurred. In addition, these epigenetic signatures are alterably adapted to and accompanying the individual stages of multistep, progressive tumorigenesis. Hence, they seem very promising for diagnosis as well as for monitoring the patient's follow-up care and even for decisions regarding personalized therapeutic options. The essential prerequisite at this approach will be a reliable methodological handling of the biological material of interest. In this study we present detailed analyses of LINE-1 DNA methylation profiles and demonstrate the sensitive detection of LINE-1 DNA methylation differences as well as between cancer patients and healthy individuals, between urinary cellular and cell-free DNA. In addition, we show methylome differences between both DNA fractions from a healthy individual and bladder cancer patients. In conclusion, we demonstrate here the unrestricted amenability of urinary cell-free DNA for both, a detailed characterization of a distinct DNA methylation alteration and its sensitive detection and a comprehensive global, array-based screening for DNA methylation differences.
    Full-text · Article · Aug 2014 · Cancer biomarkers: section A of Disease markers
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    • "Serum levels of cell-free DNA have been found in many types of cancers and are usually thought to originate from apoptotic and necrotic tumor cells (Leon et al., 1977; Stroun et al., 1989). Epigenetic modification is a universal pattern in regulating gene transcription, and methylation of tumor suppressor gene promoters is the most common epigenetic mechanism in various human tumors (Bird, 1992; Jones and Laird, 1999; Herman and Baylin, 2003; Dulaimi et al., 2004; Egger et al., 2004; Jones and Baylin, 2007; Esteller, 2008). "
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    ABSTRACT: Methylation of gene promoter CpG islands is an important early event in hepatocellular carcinoma (HCC), and detection of cell-free tumor-specific DNA methylation is becoming a useful noninvasive method for HCC. This study was aimed at determining the diagnostic value of serum insulin-like growth factor-binding protein 7 (IGFBP7) promoter methylation in hepatitis B virus-associated HCC. A total of 217 subjects, including 136 HCC patients, 46 patients with chronic hepatitis B (CHB), and 35 healthy controls (HCs), were included. The methylation status of the serum IGFBP7 gene promoter was determined using methylation-specific PCR. The frequency of serum IGFBP7 promoter methylation in HCC patients (89/136, 65%) was significantly higher than that in CHB patients (8/46, 17%; X(2) = 31.883, P < 0.001) and HCs (5/35, 14%; X(2) = 29.429, P < 0.001). Moreover, elevated IGFBP7 methylation frequency was also observed in HCC patients with vascular invasion compared with those without vascular invasion (84 versus 60%, X(2) = 6.633, P = 0.010). The sensitivities of serum IGFBP7 methylation and alpha-fetoprotein (AFP) in detecting HCC were 65 and 57%, respectively. Of note, the combination of IGFBP7 methylation and AFP showed 85% for sensitivity. These results suggest that methylation of the serum IGFBP7 gene promoter may serve as a useful noninvasive biomarker for HCC diagnosis. © 2013 Wiley Periodicals, Inc.
    Preview · Article · Jan 2014 · Genes Chromosomes and Cancer
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    • "In 1977, Leon and colleagues [2] reported that cell-free DNA (cfDNA) was present at concentrations ranging between 0 and 2 μg/mL in the serum of patients with breast cancer and that it was possible to analyze variations in the amount, depending on the stage of the disease and the response to the treatment received by the patients. In the late '80s, correlations of the presence of cfDNA in the serum of tumor patients with the malignancy of their disease were described [3]. In 1994, the potential clinical relevance of cfNAs was documented by the detection of mutated Ras molecules in the blood from patients with pancreatic cancer and myelodysplastic syndrome [4,5]. "
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    ABSTRACT: During tumor development, tumor cells release their nucleic acids into the blood circulation. This process occurs by apoptotic and necrotic cell deaths along with active cell secretion, resulting in high levels of circulating DNA, mRNA, and microRNA in the blood of patients with breast cancer. As circulating cell-free tumor nucleic acids may reflect the characteristics of the primary tumor and even of micrometastatic cells, they may be excellent blood biomarkers for screening breast cancer. Assays that allow the repetitive monitoring of patients by using blood samples as liquid biopsy may be efficient in assessing cancer progression in patients whose tumor tissue is not available. This review evaluates the recent data on the potential use of circulating cell-free nucleic acids as biomarkers for breast cancer.
    Full-text · Article · Sep 2013 · Breast cancer research: BCR
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