Circulating tumour-derived nucleic acids in cancer patients: potential applications as tumour markers

Chan, K C Allen; Lo, Yuk-ming Dennis

doi:10.1038/sj.bjc.6603625

Cited by 58 publications

(48 citation statements)

References 22 publications

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“…These low detection rates are probably related to the substantial degradation of DNA (up to 96%) caused by the bisulfite conversion step used in methylation-specific PCR (20 ) and the low concentration of circulating tumor DNA in cancer patients (21,22 ). We recently developed a nonbisulfite method for detecting and quantifying circulating hypermethylated RASSF1A sequences (11 ).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Circulating Methylated DNA as a Biomarker for Hepatocellular Carcinoma

Chan¹,

Lai²,

Mok³

et al. 2008

Clinical Chemistry

145

101

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Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Circulating Methylated DNA as a Biomarker for Hepatocellular Carcinoma

Chan¹,

Lai²,

Mok³

et al. 2008

Clinical Chemistry

145

101

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“…in plasma/serum nucleic acids of cancer patients, and have shown the potential of plasma circulating nucleic acids to be new noninvasive biomarkers in patients with various cancers (Sidransky, 1997;Anker et al, 2001;Taback and Hoon, 2004;Chan and Lo, 2007). However, during the past decade, non-coding RNAs, so-called microRNAs (miRNAs), have also been shown to regulate gene expression by targeting mRNAs for translational repression or cleavage.…”

Section: Large-scale Validation On Plasma Samplesmentioning

confidence: 99%

Circulating microRNAs in plasma of patients with gastric cancers

et al. 2010

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BACKGROUND: We examined plasma microRNA (miRNA) concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases. METHODS: We initially investigated the appropriateness of plasma miRNA assay, and then compared plasma miRNA results with the expressions in cancer tissues from eight GC patients, and also compared plasma miRNAs between pre-and post-operative paired samples from 10 GC patients. Then, plasma miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b and let-7a) were analysed in 69 GC patients and 30 healthy volunteers in total. RESULTS: The initial analysis showed that miRNAs were stable and detectable in all plasma samples, and the plasma miRNA levels reflected the tumour miRNAs in most cases. The levels of these miRNAs were significantly reduced in post-operative samples. In large-scale analysis, the plasma concentrations of miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b) were significantly higher in GC patients than controls (P ¼ 0.05, 0.006, 0.008 and o0.001 respectively), whereas let-7a was lower in GC patients (P ¼ 0.002). The values of the area under the receiver-operating characteristic curve were 0.721 for the miR-106b assay and 0.879 for the miR-106a/ let-7a ratio assay. CONCLUSION: Detection of circulating miRNAs might provide new complementary tumour markers for GC.

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“…Tumor-derived DNA sequences have been detected in the circulation of patients suffering from a wide variety of cancers (1). These tumoral DNA sequences have been further shown to be rapidly eliminated from the plasma or serum of cancer patients after tumor resection or other cancer treatments (2,3).…”

mentioning

confidence: 99%

Quantitative Analysis of the Transrenal Excretion of Circulating EBV DNA in Nasopharyngeal Carcinoma Patients

Chan

Leung²,

Yeung

et al. 2008

Clinical Cancer Research

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Purpose:The existence of transrenal clearance of circulating cell-free DNA is controversial. In this study, we used NPC as a model to investigate if circulating EBV DNA can be excreted into urine and to quantify the contribution of renal excretion to the clearance of plasma EBV DNA. Experimental Design: Quantitative analysis of urine EBV DNA was done for 74 NPC patients using real-time PCR with two different amplicon sizes. The urine concentration of EBV DNA was expressed as copies per millimole of creatinine (copies/mmol Cr) to minimize the effects of interindividual variations in hydration status. Results: EBV DNA was detectable in the urine of 56% NPC patients using a 59-bp real-time PCR assay. The median urine EBV DNA concentrations measured by the 59-and 76-bp assays were 7,040 and 290 copies/mmol Cr, respectively. Patients with detectable urine EBV DNA had significantly higher plasma concentrations, with a positive correlation between the plasma and urine concentrations of EBV DNA. The fraction of plasma EBV DNA excreted into the urine was 0.0026% of that for creatinine. Conclusions: We have shown that circulating EBV DNA can be excreted transrenally into urine in NPC patient and the fraction of excretion is negatively associated with the size of the DNA molecules. Because there is a positive correlation between plasma and urine EBV DNA concentration, urine EBV DNA analysis may potentially be applicable as an ultra-noninvasive test for the monitoring and prognostication of NPC patients.Tumor-derived DNA sequences have been detected in the circulation of patients suffering from a wide variety of cancers (1). These tumoral DNA sequences have been further shown to be rapidly eliminated from the plasma or serum of cancer patients after tumor resection or other cancer treatments (2, 3). However, the precise mechanism involved in the clearance of circulating DNA remains unclear. One possible mechanism is the transrenal excretion of circulating DNA into urine. In this regard, previous studies on the detection of transrenally excreted DNA have produced contradictory results (4 -7). The phenomenon of transrenal excretion of circulating DNA in human subjects was first described by Botezatu et al. (4) who showed the presence of Y-chromosome sequences in the urine of pregnant women carrying male fetuses and the presence of KRAS mutations in the urine of patients suffering from pancreatic and colorectal cancers. However, several other groups subsequently reported that Y-chromosome sequences were not detectable in the urine of any pregnant women carrying male fetuses, even under conditions known to increase kidney permeability (5, 7). For the detection of tumoral DNA in urine, most other reports focused on urologic cancers (8, 9), which involve the direct release of tumoral DNA into urine instead of addressing the possible transrenal excretion of circulating DNA. Interestingly, in a previous report, KRAS mutation was detected in the urine of some colorectal cancer patients who did not exhibit the corresponding ...

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Circulating tumour-derived nucleic acids in cancer patients: potential applications as tumour markers

Cited by 58 publications

References 22 publications

Quantitative Analysis of Circulating Methylated DNA as a Biomarker for Hepatocellular Carcinoma

Quantitative Analysis of Circulating Methylated DNA as a Biomarker for Hepatocellular Carcinoma

Circulating microRNAs in plasma of patients with gastric cancers

Quantitative Analysis of the Transrenal Excretion of Circulating EBV DNA in Nasopharyngeal Carcinoma Patients

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