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Cell free circulating cancer DNA

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https://www.readbyqxmd.com/read/28793862/physical-shearing-imparts-biological-activity-to-dna-and-ability-to-transmit-itself-horizontally-across-species-and-kingdom-boundaries
#1
Gorantla Venkata Raghuram, Deepika Gupta, Siddharth Subramaniam, Ashwini Gaikwad, Naveen Kumar Khare, Malcolm Nobre, Naveen Kumar Nair, Indraneel Mittra
BACKGROUND: We have recently reported that cell-free DNA (cfDNA) fragments derived from dying cells that circulate in blood are biologically active molecules and can readily enter into healthy cells to activate DNA damage and apoptotic responses in the recipients. However, DNA is not conventionally known to spontaneously enter into cells or to have any intrinsic biological activity. We hypothesized that cellular entry and acquisition of biological properties are functions of the size of DNA...
August 9, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28792880/analysis-of-plasma-epstein-barr-virus-dna-to-screen-for-nasopharyngeal-cancer
#2
K C Allen Chan, John K S Woo, Ann King, Benny C Y Zee, W K Jacky Lam, Stephen L Chan, Sam W I Chu, Constance Mak, Irene O L Tse, Samantha Y M Leung, Gloria Chan, Edwin P Hui, Brigette B Y Ma, Rossa W K Chiu, Sing-Fai Leung, Andrew C van Hasselt, Anthony T C Chan, Y M Dennis Lo
BACKGROUND: Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. METHODS: We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI)...
August 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28790338/statistical-analysis-of-mutant-allele-frequency-level-of-circulating-cell-free-dna-and-blood-cells-in-healthy-individuals
#3
Ligang Xia, Zhoufang Li, Bo Zhou, Geng Tian, Lidong Zeng, Hongyu Dai, Xiaohua Li, Chaoyu Liu, Shixin Lu, Feiyue Xu, Xiaonian Tu, Fang Deng, Yuancai Xie, Weiren Huang, Jiankui He
Cell-free DNA (cfDNA) in plasma has emerged as a potential important biomarker in clinical diagnostics, particularly in cancer. However, somatic mutations are also commonly found in healthy individuals, which interfere with the effectiveness for cancer diagnostics. This study examined the background somatic mutations in white blood cells (WBC) and cfDNA in healthy controls based on sequencing data from 821 non-cancer individuals and several cancer samples with the aim of understanding the patterns of mutations detected in cfDNA...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28778025/comparison-of-esr1-mutations-in-tumor-tissue-and-matched-plasma-samples-from-metastatic-breast-cancer-patients
#4
Takashi Takeshita, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Aiko Sueta, Keiichi Murakami, Yoko Omoto, Hirotaka Iwase
BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA) is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC) (35 tumor tissue samples and 67 plasma samples)...
July 31, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28765325/diverse-brca1-and-brca2-reversion-mutations-in-circulating-cell-free-dna-of-therapy-resistant-breast-or-ovarian-cancer
#5
Britta Weigelt, Iñaki Comino-Méndez, Ino de Bruijn, Lei Tian, Jane L Meisel, Isaac Garcia-Murillas, Charlotte Fribbens, Ros Cutts, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Salvatore Piscuoglio, Carol Aghajanian, Larry Norton, Rajmohan Murali, David M Hyman, Laetitia Borsu, Maria E Arcila, Jason Konner, Jorge S Reis-Filho, Roger A Greenberg, Mark Robson, Nicholas C Turner
Purpose: Resistance to platinum-based chemotherapy or PARP inhibition in germline BRCA1 or BRCA2 mutation carriers may occur through somatic reversion mutations or intragenic deletions that restore BRCA1 or BRCA2 function. We assessed whether BRCA1/2 reversion mutations could be identified in circulating cell-free DNA (cfDNA) of ovarian or breast cancer patients previously treated with platinum and/or PARP inhibitors. <p>Experimental Design: cfDNA from 24 prospectively accrued BRCA1- or BRCA2-germline mutant patients, including 19 platinum-resistant/refractory ovarian cancer and five platinum and/or PARP inhibitor pre-treated metastatic breast cancer patients, was subjected to massively parallel sequencing targeting all exons of 141 genes and all exons and introns of BRCA1 and BRCA2 Functional studies were performed to assess the impact of the putative BRCA1/2 reversion mutations on BRCA1/2 function...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28760909/-span-style-font-weight-400-circulating-tumor-dna-reveals-clinically-actionable-somatic-genome-of-metastatic-bladder-cancer-span
#6
Gillian R Vandekerkhove, Tilman Todenhöfer, Matti Annala, Werner J Struss, Amanda Wong, Kevin Beja, Elie Ritch, Sonal Brahmbhatt, Stas Volik, Jörg Hennenlotter, Matti Nykter, Kim N Chi, Scott North, Arnulf Stenzl, Colin C Collins, Bernhard J Eigl, Peter C Black, Alexander W Wyatt
Targeted agents and immunotherapies promise to transform the treatment of metastatic bladder cancer (BCa), but therapy selection will depend on practical tumor molecular stratification. Circulating tumor DNA (ctDNA) is established in several solid malignancies as a minimally-invasive tool to profile the tumor genome in real-time, but is critically under-explored in BCa. <p>Experimental Design: We applied a combination of whole exome sequencing and targeted sequencing across 50 BCa driver genes to plasma cell-free DNA (cfDNA) from 51 patients with aggressive BCa, including 37 with metastatic disease...
July 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28754852/molecular-characterization-of-circulating-colorectal-tumor-cells-defines-genetic-signatures-for-individualized-cancer-care
#7
Say Li Kong, Xingliang Liu, Nur-Afidah Mohamed Suhaimi, Kenneth Jia Hao Koh, Min Hu, Daniel Yoke San Lee, Igor Cima, Wai Min Phyo, Esther Xing Wei Lee, Joyce A Tai, Yu Miin Foong, Jess Honganh Vo, Poh Koon Koh, Tong Zhang, Jackie Y Ying, Bing Lim, Min-Han Tan, Axel M Hillmer
Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743887/tumor-derived-exosomes-induce-the-formation-of-neutrophil-extracellular-traps-implications-for-the-establishment-of-cancer-associated-thrombosis
#8
Ana C Leal, Daniella M Mizurini, Tainá Gomes, Natalia C Rochael, Elvira M Saraiva, Marcos S Dias, Claudio C Werneck, Micheli S Sielski, Cristina P Vicente, Robson Q Monteiro
Cancer patients are at an increased risk of developing thromboembolic complications. Several mechanisms have been proposed to explain cancer-associated thrombosis including the release of tumor-derived extracellular vesicles and the activation of host vascular cells. It was proposed that neutrophil extracellular traps (NETs) contribute to the prothrombotic phenotype in cancer. In this study, we evaluated the possible cooperation between tumor-derived exosomes and NETs in cancer-associated thrombosis. Female BALB/c mice were orthotopically injected with 4T1 breast cancer cells...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28737470/recent-advances-in-circulating-tumor-cells-and-cell-free-dna-in-metastatic-prostate-cancer-a-review
#9
Sunil Parimi, Jenny J Ko
The treatment landscape of metastatic prostate cancer has changed dramatically over the past five years. As new discoveries are made and further novel therapies become available, there is a heightened urgency to develop biomarkers that can guide prognoses and predict therapy responses. Circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) in the blood have emerged as potential promising tumor avatars. Areas covered: In this review, we describe technological breakthroughs and clinical implementation of the CTCs and ctDNA...
July 31, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28736377/-association-of-ras-mutations-in-circulating-cell-free-dna-in-the-plasma-with-clinicopathological-features-of-colorectal-cancer
#10
Jing Wu, Li-Rong Zhao, Xiu-Qiang Lin, Fen Feng, Yong-Chang Chen, Wei-Ying Deng, Yan-Ming Deng, Wei Wang
OBJECTIVE: To detect RAS mutations in the circulating cell-free DNA (cfDNA) in the plasma and explore the their correlation with the clinicopathological features in patients with colorectal cancer. METHODS: Real-time PCR was used to detect RAS mutations in plasma cfDNA and matched tumor tissue DNA samples from 71 colorectal cancer patients. The correlation of RAS mutations with the clinicopathological features of the patients were analyzed. RESULTS: Of the 71 patients with colorectal cancer, 23 (32...
July 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28732213/comparison-of-blood-collection-tubes-from-three-different-manufacturers-for-the-collection-of-cell-free-dna-for-liquid-biopsy-mutation-testing
#11
Christina Alidousty, Danielle Brandes, Carina Heydt, Svenja Wagener, Maike Wittersheim, Stephan Christian Schäfer, Barbara Holz, Sabine Merkelbach-Bruse, Reinhard Büttner, Jana Fassunke, Anne Maria Schultheis
The improvement in sensitive techniques has allowed the detection of tumor-specific aberrations in circulating tumor (ct) DNA. Amplification-refractory mutation system PCR has been used for the analysis of ctDNA to detect resistance-causing mutations in the epidermal growth factor receptor gene (eg, EGFR T790M) in lung cancer patients. So far, Streck tubes have been widely used as standard blood collection tubes. Here, we compared blood collection tubes manufactured by Streck with tubes from Roche and Qiagen regarding their utility in stabilizing ctDNA in plasma samples...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28723513/the-natural-history-and-outcome-predictors-of-metastatic-castration-resistant-prostate-cancer
#12
REVIEW
Robert J van Soest, Jason A Efstathiou, Cora N Sternberg, Bertand Tombal
CONTEXT: Biomarkers for the treatment of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed by clinicians to facilitate treatment decisions. OBJECTIVE: To review current prognostic and predictive biomarkers in mCRPC. EVIDENCE ACQUISITION: We performed a nonsystematic review of the literature from 2004 to August 2016 by searching in Medline. Cross-matching references were used to search for additional articles. We reviewed clinical research and review articles written in the English language...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723342/molecular-analysis-of-circulating-free-dna-from-lung-cancer-patients-in-routine-laboratory-practice-a-cross-platform-comparison-of-three-different-molecular-methods-for-mutation-detection
#13
Stephan Bartels, Sascha Persing, Britta Hasemeier, Elisa Schipper, Hans Kreipe, Ulrich Lehmann
Cell-free DNA (cfDNA), which is isolated from blood plasma, represents a noninvasive source for the detection of mutations conferring resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small-cell lung cancer patients. In advanced disease stages, performing regular biopsies is often not possible because of the general health condition of the patients. Furthermore, a biopsy of a single tumor lesion or metastasis may not reflect the heterogeneous genotype of the tumor and its metastases...
July 16, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28720677/synthetic-circulating-cell-free-dna-as-quality-control-materials-for-somatic-mutation-detection-in-liquid-biopsy-for-cancer
#14
Rui Zhang, Rongxue Peng, Ziyang Li, Peng Gao, Shiyu Jia, Xin Yang, Jiansheng Ding, Yanxi Han, Jiehong Xie, Jinming Li
BACKGROUND: Detection of somatic genomic alterations in tumor-derived cell-free DNA (cfDNA) in the plasma is challenging owing to the low concentrations of cfDNA, variable detection methods, and complex workflows. Moreover, no proper quality control materials are available currently. METHODS: We developed a set of synthetic cfDNA quality control materials (SCQCMs) containing spike-in cfDNA on the basis of micrococcal nuclease digestion carrying somatic mutations as simulated cfDNA and matched genomic DNA as genetic background to emulate paired tumor-normal samples in real clinical tests...
July 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28693156/detection-of-opcml-methylation-a-possible-epigenetic-marker-from-free-serum-circulating-dna-to-improve-the-diagnosis-of-early-stage-ovarian-epithelial-cancer
#15
Bi Wang, Lei Yu, Xin Luo, Lin Huang, Qin-Shan Li, Xiao-Shan Shao, Yi Liu, Yu Fan, Guo-Zhen Yang
The aim of the present study was to identify the appropriate DNA sequence and design high-quality primers for methylation-specific polymerase chain reaction (MSP). These primers may be used to examine and identify patients with early-stage epithelial ovarian carcinoma (EOC). Opioid binding protein/cell adhesion molecule like (OPCML), Runt-related transcription factor 3 and tissue factor pathway inhibitor 2 were selected as possible molecular markers. MSP primer sets were designed to monitor the methylation of the three markers...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28683468/correlation-between-circulating-mutant-dna-and-metabolic-tumour-burden-in-advanced-non-small-cell-lung-cancer-patients
#16
Anne Winther-Larsen, Christina Demuth, Joan Fledelius, Anne Tranberg Madsen, Karin Hjorthaug, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival. METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28679775/detection-of-activating-estrogen-receptor-gene-esr1-mutations-in-single-circulating-tumor-cells
#17
Carmela Paolillo, Zhaomei Mu, Giovanna Rossi, Matthew J Schiewer, Thomas Nguyen, Laura Austin, Ettore Capoluongo, Karen E Knudsen, Massimo Cristofanilli, Paolo Fortina
Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). <br /><br />Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hot spot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch(®) and DEPArray™ technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28679646/multiplexed-elimination-of-wild-type-dna-and-high-resolution-melting-prior-to-targeted-resequencing-of-liquid-biopsies
#18
Ioannis Ladas, Mariana Fitarelli-Kiehl, Chen Song, Viktor A Adalsteinsson, Heather A Parsons, Nancy U Lin, Nikhil Wagle, G Mike Makrigiorgos
BACKGROUND: The use of clinical samples and circulating cell-free DNA (cfDNA) collected from liquid biopsies for diagnostic and prognostic applications in cancer is burgeoning, and improved methods that reduce the influence of excess wild-type (WT) portion of the sample are desirable. Here we present enrichment of mutation-containing sequences using enzymatic degradation of WT DNA. Mutation enrichment is combined with high-resolution melting (HRM) performed in multiplexed closed-tube reactions as a rapid, cost-effective screening tool before targeted resequencing...
July 5, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28676213/urine-circulating-tumor-dna-ctdna-detection-of-acquired-egfr-t790m-mutation-in-non-small-cell-lung-cancer-an-outcomes-and-total-cost-of-care-analysis
#19
Jacob Sands, Qianyi Li, John Hornberger
OBJECTIVES: Third-generation tyrosine kinase inhibitors (TKIs) have proven effective in patients with the acquired EGFR T790M resistance mutation who progress on prior EGFR TKI therapy. Median progression-free survival (PFS) on a 3rd-gen TKI was 9-10 months for T790M+ patients compared to 2.8 months for T790M- patients. PFS is similar regardless of the specimen used to assess T790M, such as tissue, plasma, or urine ctDNA. This study aimed to assess the total cost of care of a urine-testing strategy (UTS) versus a tissue-testing strategy (TTS) for T790M detection, in patients with EGFR-mutation positive lung adenocarcinoma and progression on prior TKI therapy...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28672797/integrity-and-quantity-of-total-cell-free-dna-in-the-diagnosis-of-thyroid-cancer-correlation-with-cytological-classification
#20
Francesca Salvianti, Corinna Giuliani, Luisa Petrone, Irene Mancini, Vania Vezzosi, Cinzia Pupilli, Pamela Pinzani
Cell-free DNA (cfDNA) quantity and quality in plasma has been investigated as a non-invasive biomarker in cancer. Previous studies have demonstrated increased cfDNA amount and length in different types of cancer with respect to healthy controls. The present study aims to test the hypothesis that the presence of longer DNA strands circulating in plasma can be considered a biomarker for tumor presence in thyroid cancer. We adopted a quantitative real-time PCR (qPCR) approach based on the quantification of two amplicons of different length (67 and 180 bp respectively) to evaluate the integrity index 180/67...
June 24, 2017: International Journal of Molecular Sciences
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