The Origin of Circulating Free DNA

Vaart, Maniesh van der; Pretorius, P. J.

doi:10.1373/clinchem.2007.092734

Cited by 143 publications

(127 citation statements)

References 4 publications

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“…In general, cell-free DNA fragments in healthy individuals are small and uniform, and mainly originate from normal cell apoptosis. However, in cancer patients, cell-free DNA fragments are usually incomplete and random, with different fragment lengths, and are considered to originate from necrosis of tumor cells (13). A high concentration of tumor-associated cell-free DNA and high mutant KRAS levels are related to poor prognosis, outcome and recurrence risk in patients with colorectal cancer (14).…”

Section: Introductionmentioning

confidence: 99%

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

Sun

Zhu

et al. 2013

Oncology Reports

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Abstract. In the present study, we studied the relationship between plasma cell-free DNA and the effect of preoperative chemoradiotherapy in patients with rectal cancer. The concentration, KRAS mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status of cell-free DNA were measured by using polymerase chain reaction (PCR) analyses. The response to chemoradiotherapy was assessed using tumor regression grading (TRG) scores. The cell-free DNA concentrations in patients with rectal cancer (n=34) were significantly higher compared to healthy controls (n=10). The 400-base pair (bp) DNA concentration, 400-/100-bp DNA ratio decreased significantly after chemoradiotherapy in the good response group. The incidence of KRAS mutation decreased significantly after chemoradiotherapy in both good and poor response groups. Higher MGMT promoter methylation status at baseline DNA was associated with a better tumor response. Therefore, cell-free DNA detection may be useful in evaluating the effect of preoperative chemoradiotherapy in patients with rectal cancer.

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Section: Introductionmentioning

confidence: 99%

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

Sun

Zhu

et al. 2013

Oncology Reports

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“…In cancer, it has been demonstrated that tumor cells may release genomic DNA into the blood, being apoptosis and necrosis of tumor cells the leading mechanisms of DNA release (11)(12)(13). Several studies have reported that NSCLC patients have higher levels of cfDNA in the blood compared to healthy controls or patients with benign disease (14,15).…”

mentioning

confidence: 99%

Liquid biopsy in early stage lung cancer

Pérez-Ramírez¹,

Cañadas-Garre²,

Robles³

et al. 2016

Transl. Lung Cancer Res.

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“…Urinary DNA derives from either cell-free DNA originating from apoptotic or-, necrotic urothelial, tumor or bloodderived cells [5,6] or from intact cells shed into urine, such as exfoliated tumor cells [7], normal uroepithelial cells and leukocytes. Depending on the circumstances, tumor cell DNA could be enriched in either one or both DNA fractions.…”

Section: Introductionmentioning

confidence: 99%

“…Novel potent biomarkers may detect these malignancies earlier and with greater accuracy and may even help to discriminate between various tumor subclasses, a step further towards individualized medicine. Thus, they could contribute as well to improve the therapeutic success.Urinary DNA derives from either cell-free DNA originating from apoptotic or-, necrotic urothelial, tumor or bloodderived cells [5,6] or from intact cells shed into urine, such as exfoliated tumor cells [7], normal uroepithelial cells and leukocytes. Depending on the circumstances, tumor cell DNA could be enriched in either one or both DNA fractions.…”

mentioning

confidence: 99%

Methods for Separate Isolation of Cell-Free DNA and Cellular DNA from Urine-Application of Methylation-Specific PCR on both DNA Fractions

Beermann¹,

Ghanjati²,

Hermanns³

et al. 2011

TOBIOMJ

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Abstract:The analysis of genomic DNA is widely-used for research, forensic and diagnostic purposes. Here we describe reliable methods for isolation of cell-free DNA and cellular DNA from urine. Both DNA fractions are suitable for PCR and Methylation-Specific PCR (MSP) amplification, leading to consistent and reproducible results. A kinetics analysis describes the decline of efficiency of MSP performed with urinary DNA which had been stored at room temperature with and without proteinase K for various time periods.Keywords: Cell-free DNA, Diagnosis, DNA methylation, Urine.For research purposes, DNA is frequently required in order to determine genetic variability in defined populations and to identify genomic and epigenomic alterations in disease. In forensic science, DNA analyses aid enquiries associated with criminal offenses and missing persons investigations, often based on trace amounts of genetic material [1]. Forensic scientists frequently utilize repetitive DNA elements for gender and species identification or inference of human ancestry [2]. An emerging application of DNA-based assays is disease diagnostics, including the diagnosis of bladder and prostate cancers, the main urological causes of morbidity and mortality worldwide [3,4]. Novel potent biomarkers may detect these malignancies earlier and with greater accuracy and may even help to discriminate between various tumor subclasses, a step further towards individualized medicine. Thus, they could contribute as well to improve the therapeutic success.Urinary DNA derives from either cell-free DNA originating from apoptotic or-, necrotic urothelial, tumor or bloodderived cells [5,6] or from intact cells shed into urine, such as exfoliated tumor cells [7], normal uroepithelial cells and leukocytes. Depending on the circumstances, tumor cell DNA could be enriched in either one or both DNA fractions. Therefore, proper differentiation between cell-free DNA released from disintegrated cells and DNA of intact cells in urine could add an additional value for diagnostic purposes. Basic prerequisites for use in diagnostics are an appropriate amount of each DNA fraction and sufficient quality for successful application in various PCR amplification procedures. In particular, altered DNA methylation is commonly found in urological malignancies [8,9] and should represent a useful source of beneficial biomarkers. DNA, and especially *Address correspondence to this author at the Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Düsseldorf, Germany; Tel: +49-(0)211-81-16905; Fax: +49-(0)-211-81-04543; E-mail: santourlidis@itz.uni-duesseldorf.de # contributed equally.cell-free DNA isolated from urine should therefore be suitable for Methylation Specific PCR which includes bisulfite treatment, a routine technical step, which is inevitably associated with some chemically-induced degradation of the genetic material with diminished PCR efficiency as a consequence.Voided native urine is transferred into a 50 ml sample tube and is imme...

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The Origin of Circulating Free DNA

Cited by 143 publications

References 4 publications

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

Liquid biopsy in early stage lung cancer

Methods for Separate Isolation of Cell-Free DNA and Cellular DNA from Urine-Application of Methylation-Specific PCR on both DNA Fractions

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