scholarly journals Rapid and ultrasensitive electrochemical detection of circulating tumor DNA by hybridization on the network of gold-coated magnetic nanoparticles

2021 ◽  
Author(s):  
Dongfei Chen ◽  
Yanfang Wu ◽  
Sharmin Hoque ◽  
Richard D. Tilley ◽  
J. Justin Gooding

This study introduces a new electrochemical sensing strategy for the rapid detection of circulating tumor DNA (ctDNA) from whole blood in combination with a network of DNA-Au@MNPs with high sensitivity and excellent selectivity.

2020 ◽  
Vol 12 (4) ◽  
pp. 440-447 ◽  
Author(s):  
Mahbubur Rahman ◽  
Daxiang Cui ◽  
Shukui Zhou ◽  
Amin Zhang ◽  
Di Chen

A high-performance electrochemical sensing platform inspired by a functional ‘green’ electrochemical reduction pathway was developed to identify and detect circulating tumor DNA (ctDNA) of gastric carcinoma in peripheral blood.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii15-ii15
Author(s):  
Farshad Nassiri ◽  
Ankur Chakravarthy ◽  
Shengrui Feng ◽  
Roxana Shen ◽  
Romina Nejad ◽  
...  

Abstract BACKGROUND The diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Non-invasive diagnostic approaches, particularly for patients with brain tumours, provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. We reasoned that DNA methylation profiles of circulating tumor DNA in blood can be used as a clinically useful biomarker for patients with brain tumors, given the specificity of DNA methylation profiles for cell-of-origin. METHODS We generated methylation profiles on the plasma of 608 patients with cancer (219 intracranial, 388 extracranial) and 60 healthy controls using a cell-free methylated DNA immunoprecipitation combined with deep sequencing (cfMeDIP-seq) approach. Using machine-learning approaches we generated and evaluated models to distinguish brain tumors from extracranial cancers that may metastasize to the brain, as well as additional models to discriminate common brain tumors included in the differential diagnosis of solitary extra-axial and intra-axial tumors. RESULTS We observed high sensitivity and discriminative capacity for our models to distinguish gliomas from other cancerous and healthy patients (AUC=0.99, 95%CI 0.96–1), with similar performance in IDH mutant and wildtype gliomas as well as in lower- and high-grade gliomas. Excluding non-malignant contributors to plasma methylation did not change model performance (AUC=0.982, 95%CI 0.93–1). Models generated to discriminate intracranial tumors from each other also demonstrated high accuracy for common extra-axial tumors (AUCmeningioma=0.89, 95%CI 0.80–0.97; AUChemangiopericytoma=0.95, 95%CI 0.73–1) as well as intra-axial tumors ranging from low-grade indolent glial-neuronal tumors (AUC 0.93, 95%CI 0.80 – 1) to diffuse intra-axial gliomas with distinct molecular composition (AUCIDH-mutant glioma = 0.82, 95%CI 0.66 -0.98; AUCIDH-wildtype-glioma = 0.71, 95%CI 0.53 – 0.9). Plasma cfMeDIP-seq signals originated from corresponding tumor tissue DNA methylation signals (r=0.37, p< 2.2e-16). CONCLUSIONS These results demonstrate the potential for cfMeDIP-seq profiles to not only detect circulating tumor DNA, but to accurately discriminate common intracranial tumors that share cell-of-origin lineages.


Author(s):  
Zhijia Peng ◽  
Xiaogang Lin ◽  
Weiqi Nian ◽  
Xiaodong Zheng ◽  
Jayne Wu

Early diagnosis and treatment have always been highly desired in the fight against cancer, and detection of circulating tumor DNA (ctDNA) has recently been touted as highly promising for early cancer screening. Consequently, the detection of ctDNA in liquid biopsy gains much attention in the field of tumor diagnosis and treatment, which has also attracted research interest from the industry. However, traditional gene detection technology is difficult to achieve low cost, real-time and portable measurement of ctDNA. Electroanalytical biosensors have many unique advantages such as high sensitivity, high specificity, low cost and good portability. Therefore, this review aims to discuss the latest development of biosensors for minimal-invasive, rapid, and real-time ctDNA detection. Various ctDNA sensors are reviewed with respect to their choices of receptor probes, detection strategies and figures of merit. Aiming at the portable, real-time and non-destructive characteristics of biosensors, we analyze their development in the Internet of Things, point-of-care testing, big data and big health.


2017 ◽  
Vol 12 (11) ◽  
pp. S1843-S1844 ◽  
Author(s):  
A. Ruiz-Valdepenas ◽  
K. Heider ◽  
G. Doughton ◽  
W. Qian ◽  
C. Massie ◽  
...  

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 604-604
Author(s):  
Kanwal Pratap Singh Raghav ◽  
Rona Yaeger ◽  
Jonathan M. Loree ◽  
Arvind Dasari ◽  
Van K. Morris ◽  
...  

604 Background: Amps, as oncogenic and resistance drivers, have therapeutic implications, but unlike mutations, have been sparsely described in mCRC. Functional account is piecemeal due to vague definitions, limited data on co-occurring alterations and use of primary tissue samples nonrepresentative of tumor heterogeneity. Our aim was to define the amp landscape in mCRC using tissue and ctDNA sequencing. Methods: We performed systematic analyses of copy-number variation in 2 cohorts of mCRC patients (pts) [tissue (TC) (N = 1,134) and ctDNA (BC) (N = 3,218)] who had high sensitivity targeted sequencing with MSK-IMPACT (341-468 genes) or Guardant Health (70-73 genes) panel, respectively. For BC, plasma copy number was adjusted (ApCN) to account for variable tumor DNA shedding using max allele frequency and high amp (HAmp) was defined as > 4 copies (similar to predefined tissue cutoff). Results: 166 (15%) and 405 (13%) pts in TC and BC harbored amp in at least one of 18 genes assessed by both panels (Table). Amp prevalence for individual gene was similar in both cohorts ( r = 0.9; P < .01) with RTK amps ( EGFR, ERBB2, MET, FGFR1/2, PDGFRA) seen in 8% pts. Key RTK amps were enriched in RAS/BRAF wild type (RB WT) compared to mutant (RB MUT) (OR 3.5; P < .01) pts in both cohorts, in contrast to low prevalence RTK and non-RTK amps. Median ApCN was higher for RTKs in RB WT vs MUT cases ( ERBB2: 12 vs 5; P = .02). Using validated EGFRab exposure (EGFRi) ctDNA signature, we found that EGFRi pts had higher prevalence of EGFR, MET, BRAF, KRAS, PIK3CA and FGFR1 amps compared to EGFRab naïve pts. Conclusions: While individually uncommon, amps occur across key oncogenic pathways in mCRC and after adjusting for ctDNA shedding, are seen at similar prevalence in tissue and plasma. Amps in RTKs are seen in 10-12% of RB WT tumors, suggesting clinically relevant roles as oncogenic effectors and targets. After EGFRi, a number of amps emerge, including PIK3CA and FGFR1 amps, not previously implicated in acquired resistance. [Table: see text]


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