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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    • "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.
    Genes Chromosomes and Cancer 01/2014; 53(1). DOI:10.1002/gcc.22120 · 4.04 Impact Factor
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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.
    Breast cancer research: BCR 09/2013; 15(5):211. DOI:10.1186/bcr3446 · 5.49 Impact Factor
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    • "In addition to progress in CTC research, significant advancement has also been made with ctDNA. The presence of small amounts of tumor DNA in the plasma of cancer patients was demonstrated several decades ago [64-67]. Since then, multiple studies have investigated plasma DNA's potential as a biomarker (for a detailed review see [68]). "
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    ABSTRACT: For cancer patients, the current approach to prognosis relies on clinicopathological staging, but usually this provides little information about the individual response to treatment. Therefore, there is a tremendous need for protein and genetic biomarkers with predictive and prognostic information. As biomarkers are identified, the serial monitoring of tumor genotypes, which are instable and prone to changes under selection pressure, is becoming increasingly possible. To this end, circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) shed from primary and metastatic cancers may allow the non-invasive analysis of the evolution of tumor genomes during treatment and disease progression through 'liquid biopsies'. Here we review recent progress in the identification of CTCs among thousands of other cells in the blood and new high-resolution approaches, including recent microfluidic platforms, for dissecting the genomes of CTCs and obtaining functional data. We also discuss new ctDNA-based approaches, which may become a powerful alternative to CTC analysis. Together, these approaches provide novel biological insights into the process of metastasis and may elucidate signaling pathways involved in cell invasiveness and metastatic competence. In medicine these liquid biopsies may emerge to be powerful predictive and prognostic biomarkers and could therefore be instrumental for areas such as precision or personalized medicine.
    Genome Medicine 08/2013; 5(8):73. DOI:10.1186/gm477 · 5.34 Impact Factor
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