Neoplastic characteristics of the DNA found in the plasma of cancer patients
ABSTRACT 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). "
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 · 3.84 Impact Factor
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- "BRAF V600E mutation is examined in the case of a negative KRAS mutation status in several national guidelines, thus enlarging the targeted therapy–resistant patient population stratum. Significant amounts of circulating cell–free DNA (ccfDNA) are present in the plasma of cancer patients  . As blood analysis of ccfDNA is easy to set up and relatively noninvasive, ccfDNA represents a very attractive tool for detecting the presence of mutations. "
ABSTRACT: We used a novel method based on allele-specific quantitative polymerase chain reaction (Intplex) for the analysis of circulating cell.free DNA (ccfDNA) to compare total ccfDNA and KRAS- or BRAF-mutated ccfDNA concentrations in blood samples from mice xenografted with the human SW620 colorectal cancer (CRC) cell line and from patients with CRC. Intplex enables single-copy detection of variant alleles down to a sensitivity of ≥0.005 mutant to wild-type ratio. The proportion of mutant allele corresponding to the percentage of tumor-derived ccfDNA was elevated in xenografted mice with KRAS homozygous mutation and varied highly from 0.13% to 68.7% in samples from mutation-positive CRC patients (n = 38). Mutant ccfDNA alleles were quantified in the plasma of every patient at stages II/III and IV with a mean of 8.4% (median, 8.4%) and 21.8% (median, 12.4%), respectively. Twelve of 38 (31.6%) and 5 of 38 (13.2%) samples showed a mutation load higher than 25%and 50%, respectively. This suggests that an important part of ccfDNA may originate from tumor cells. In addition, we observed that tumor-derived (mutant) ccfDNA was more fragmented than ccfDNA from normal tissues. This observation suggests that the form of tumor-derived and normal ccfDNA could differ. Our approach revealed that allelic dilution is much less pronounced than previously stated, considerably facilitating the noninvasive molecular analysis of tumors.Translational oncology 06/2013; 6(3):319-28. DOI:10.1593/tlo.12445 · 3.40 Impact Factor
Biomarker, 03/2012; , ISBN: 978-953-51-0577-0
- "To date, a number of studies show that plasma and serum nucleic acids can serve as both tumor-and fetal-specific markers for cancer detection and prenatal diagnosis, respectively. For example, several studies reported increased concentrations of DNA in the plasma or serum of cancer patients sharing some characteristics with DNA of tumor cells (Leon et al., 1977; Stroun et al., 1989). Interestingly, DNA levels decreased by up to 90% after radiotherapy, while persistently high or increasing DNA concentrations were associated with a lack of response to treatment (Anker et al., 2001). "