Circulating Nucleic Acids as a Potential Source for Cancer Biomarkers

Vlassov, Valentin V.; Laktionov, Pavel P.; Rykova, Elena Y.

doi:10.2174/156652410790963295

Cited by 97 publications

(48 citation statements)

References 170 publications

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“…Recent studies have shown that aberrant DNA methylation, which typically occurs before patients develop clinical manifestations and radiographic evidence, can be detected in cellfree serum (Vlassov et al, 2010;Liggett et al, 2011;Zhang et al, 2013). The amount of available cell-free serum DNA is often very low.…”

Section: Discussionmentioning

confidence: 99%

Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Xing¹,

Tang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. DNA methylation plays an important role in carcinogenesis and cancer development. In this study, we examined gene methylation in epithelial ovarian cancer (EOC) using cationic conjugated polymer (CCP)-based fluorescence resonance energy transfer (FRET) to evaluate the application of cumulative methylation alternations of genes associated with cancer antigen 125 for early cancer diagnosis. The methylation status of 3 genes (Ras association domain family 1 isoform A, RASSF1A; opioid-binding protein/cell adhesion molecule, OPCML; homeobox A9, HOXA9) were examined and compared in 35 EOC samples and 11 normal ovarian tissue samples using CCP-based FRET. Gene methylation levels were clustered into 3 sections and assigned a value; values for the 3 genes were summed. Although methylation of the OPCML gene was significantly associated with stage, histological types, grade, and ascites and that of RASSF1A and HOXA9 was not, the sum for the 3 genes was significantly associated with stage and ascites. The sum showed higher sensitivity (85.7%) and specificity (100%) for discriminating EOC from normal ovarian tissues than did the methylation status of RASSF1A, OPCML, and HOXA9

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Section: Discussionmentioning

confidence: 99%

Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Xing¹,

Tang

et al. 2015

Genet. Mol. Res.

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“…DNA methylation is being tested as potential diagnostic marker for a variety of cancers such as prostate, colorectal, cervical, lung, bladder cancer and leukemias. [39][40][41][42][43] Whereas hypermethylation of tumor suppressor genes is a widely accepted mechanism for tumor progression, DNA hypermethylation in response to UTI infection is currently an understudied field and no DNA methylation based biomarker for future UTI infection susceptibility exists. Our goal is to identify candidate regions as potential biomarkers for UTI proclivity, as well as reveal new candidate mechanisms associated with UTI pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Uropathogenic E. coli infection provokes epigenetic downregulation of CDKN2A (p16INK4A) in uroepithelial cells

Tölg

Sabha

Cortese

et al. 2011

Laboratory Investigation

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Host cell and bacterial factors determine severity and duration of infections. To allow for bacteria pathogenicity and persistence, bacteria have developed mechanisms that modify expression of host genes involved in cell cycle progression, apoptosis, differentiation and the immune response. Recently, Helicobacter pylori infection of the stomach has been correlated with epigenetic changes in the host genome. To identify epigenetic changes during Escherichia coli induced urinary tract infection (UTI), we developed an in vitro model of persistent infection of human uroepithelial cells with uropathogenic E. coli (UPEC), resulting in intracellular bacteria colonies. Cells inoculated with FimH-negative E. coli (N-UPEC) that are not internalized and non-inoculated cells were used as controls. UPEC infection significantly induced de novo methyltransferase (DNMT) activity (12.5-fold P ¼ 0.002 UPEC vs non-inoculated and 250-fold P ¼ 0.001 UPEC vs N-UPEC inoculated cells) and Dnmt1 RNA expression (6-fold P ¼ 0.04 UPEC vs non-inoculated cells) compared with controls. DNMT1 protein levels were significantly increased in three uroepithelial cell lines (5637, J82, HT-1197) in response to UPEC infection as demonstrated by confocal analysis. Real-time PCR analysis of candidate genes previously associated with bacteria infection and/or innate immunity, revealed UPEC-induced downregulation of the tumor suppressor gene CDKN2A (3.3-fold P ¼ 0.007 UPEC vs non-inoculated and 3.3-fold P ¼ 0.001 UPEC vs N-UPEC) and the DNA repair gene MGMT (9-fold P ¼ 0.03 UPEC vs non-inoculated). Expression of CDH1, MLH1, DAPK1 and TLR4 was not affected. Pyrosequencing of CDKN2A and MGMT CpG islands revealed increased methylation in CDKN2A exon 1 (3.8-fold P ¼ 0.04 UPEC vs N-UPEC and UPEC vs non-inoculated). Methylation of MGMT was not affected. UPEC-induced methylation of CDKN2A exon 1 may increase bladder cancer and presage UTI risk, and be useful as a biological marker for UTI susceptibility or recurrence.

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“…RF, reference; ARMS, amplification refractory mutation system; qPCR, quantitative polymerase chain reaction. general rule, the mismatched bases are often designed in the last 3 bp of the ARMS primer to discriminate between the wild-type and the mutant alleles (26)(27)(28). Notably, in the present study, the rs1050171 was observed to be located in the eighth base from the 3' end of the ARMS primer, and the results revealed that it really affected the sensitivity of T790M mutation detection, particularly in samples with low mutation rates.…”

Section: Discussionmentioning

confidence: 57%

Exploring the impact of EGFR T790M neighboring SNPs on ARMS-based T790M mutation assay

Duan

Lou

et al. 2016

Oncology Letters

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Abstract. The present study aimed to explore the influence of T790M neighboring single nucleotide polymorphism (SNP) on the sensitivity of amplification refractory mutation system (ARMS)-based T790M mutation assay. Three ARMS-quantitative polymerase chain reaction (qPCR) systems (system 1 had a forward ARMS primer without rs1050171, system 2 included a forward ARMS primer with rs1050171 and system 3 contained the above two forward ARMS primers) were used to detect the T790M mutation in two series plasmid samples and genomic DNA (gDNA) of the cell line H1975. A total of 670 formalin-fixed paraffin-embedded (FFPE) tumor samples from non-small cell lung cancer patients were used to detect the epidermal growth factor receptor (EGFR) gene T790M mutation by direct sequencing and ARMS-qPCR. The ARMS-qPCR system 1 effectively detected samples with as low as 1% T790M mutant plasmid 1 (without rs1050171) and with 50% T790M mutant plasmid 2 (with rs1050171), while the ARMS-qPCR system 2 detected samples with 20 and 50% T790M mutant plasmid 1, in addition to samples with 1% T790M mutant plasmid 2. For the ARMS-qPCR system 3, samples with as low as 1% T790M mutant plasmids 1 or 2 were effectively detected. For gDNA analysis of the cell line H1975, the T790M mutation was effectively detected by the ARMS-qPCR systems 2 and 3 (~50% mutation rate), but was detected with a low mutation abundance by the ARMS-qPCR system 1 (~1% mutation rate). Of the 670 FFPE samples, 5 cases were identified to have the T790M mutation by sequencing and by the ARMS-qPCR system 1. One sample (named N067), which was considered as T790M-negative by sequencing, was demonstrated to have the T790M mutation using the ARMS-qPCR system 1. Sample N094, which was variant homozygous for rs1050171 and was indicated to be T790M-negative by sequencing and by the ARMS-qPCR system 1, was identified to have the T790M mutation with the ARMS-qPCR system 3. The A-variant allele frequency of rs1050171 was observed to be 28.2% in the 670 FFPE tumor samples, while the presence of rs148188503 (c. C2355T, p. T785T) was observed in sample N558, and a novel SNP with a base substitution (c. T2375C) at position 792 (p. L792P) in exon 20 of the EGFR gene was observed in sample N310. rs1050171 is a high-frequency SNP located near T790M, and the mutation statuses of rs1050171 appear to influence the sensitivity of the ARMS-based T790M detection system, thus generating a 14.3% false-negative rate (1/7). The present study proposes the risk that target neighboring SNPs (as far as 8 bp away in the present study) may exert on the sensitivity of ARMS-based detection methods. IntroductionThe use of reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, which function by competitively binding at the adenosine triphosphate-binding cleft of the receptor kinase domain of EGFR and consequently blocking the kinase activation and subsequent downstream signal transduction processes, produces secondary resistance in the majority of ...

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Circulating Nucleic Acids as a Potential Source for Cancer Biomarkers

Cited by 97 publications

References 170 publications

Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Uropathogenic E. coli infection provokes epigenetic downregulation of CDKN2A (p16INK4A) in uroepithelial cells

Exploring the impact of EGFR T790M neighboring SNPs on ARMS-based T790M mutation assay

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