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cfDNA NGS

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https://www.readbyqxmd.com/read/29137355/a-pilot-study-evaluating-concordance-between-blood-based-and-patient-matched-tumor-molecular-testing-within-pancreatic-cancer-patients-participating-in-the-know-your-tumor-kyt-initiative
#1
Michael J Pishvaian, R Joseph Bender, Lynn M Matrisian, Lola Rahib, Andrew Hendifar, William A Hoos, Sam Mikhail, Vincent Chung, Vincent Picozzi, Craig Heartwell, Kimberly Mason, Katelyn Varieur, Metasebia Aberra, Subha Madhavan, Emanuel Petricoin, Jonathan R Brody
Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRB-approved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110843/frequency-and-clinical-impact-of-preoperative-circulating-tumor-cells-in-resectable-non-metastatic-lung-adenocarcinomas
#2
Nadia Dandachi, Verena Tiran, Joerg Lindenmann, Luka Brcic, Nicole Fink-Neuboeck, Karl Kashofer, Gudrun Absenger, Angelika Bezan, Richard J Cote, Ram Datar, Marija Balic
OBJECTIVES: Despite successful surgery, 30-50% of patients with resectable non-small cell lung cancer develop tumor recurrence within 5 years of surgery. MATERIALS AND METHODS: In this prospective study, we performed CTC enumerations in 40 patients with non-metastatic lung adenocarcinoma (NMLA) using a size-based microfilter. Additionally, cfDNA isolated from plasma was analyzed in 35 out of 40 patients. RESULTS: CTCs were identified in 15 out of 40 patients (37...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29051321/liquid-biopsies-using-plasma-exosomal-nucleic-acids-and-plasma-cell-free-dna-compared-with-clinical-outcomes-of-patients-with-advanced-cancers
#3
Lino Möhrmann, Helen Huang, David S Hong, Apostolia M Tsimberidou, Siqing Fu, Sarina Piha-Paul, Vivek Subbiah, Daniel D Karp, Aung Naing, Anne K Krug, Daniel Enderle, Tina Priewasser, Mikkel Noerholm, Erez Eitan, Christine Coticchia, Georg Stoll, Lisa-Marie Jordan, Cathy Eng, Scott Kopetz, Johan Skog, Funda Meric-Bernstam, Filip Janku
PURPOSE: Blood-based liquid biopsies offer easy access to genomic material for molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates from dying cells. Exosomal nucleic acids (exoNA) originate from living cells, which can better reflect underlying cancer biology. EXPERIMENTAL DESIGN: Next-generation sequencing (NGS) was used to test exosomal nucleic acids (exoNA), and droplet digital PCR (ddPCR) and BEAMing PCR were used to test cfDNA for BRAF V600, KRAS G12/G13, and EGFR exon19del/L858R mutations in 43 patients with progressing advanced cancers...
October 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28973495/identification-of-mutations-in-cell-free-circulating-tumor-dna-in-adrenocortical-carcinoma-a-case-series
#4
Sara G Creemers, Esther Korpershoek, Peggy N Atmodimedjo, Winand N M Dinjens, Peter M van Koetsveld, Richard A Feelders, Leo J Hofland
Context: The disease course of adrenocortical carcinoma (ACC) patients is heterogeneous. A marker for prognosis and treatment response would facilitate choices for diagnosis and therapy. In other cancer types, circulating cell-free tumor DNA predicted tumor dynamics. Case Descriptions: The present pilot study included six patients. Next-generation sequencing (NGS) showed mutations in three ACC cases. From these patients, blood was drawn before (1 to 2 weeks) and after surgery and cell-free circulating DNA (cfDNA) was isolated...
October 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28949453/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#5
(no author information available yet)
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28947568/discrimination-of-germline-egfr-t790m-mutations-in-plasma-cell-free-dna-allows-study-of-prevalence-across-31-414-cancer-patients
#6
Yuebi Hu, Ryan S Alden, Justin I Odegaard, Stephen R Fairclough, Ruthia Chen, Jennifer Heng, Nora Feeney, Rebecca Nagy, Jayshree Shah, Bryan Ulrich, Martin Gutierrez, Richard B Lanman, Judy E Garber, Cloud P Paweletz, Geoffrey R Oxnard
PURPOSE: Plasma cell-free DNA (cfDNA) analysis is increasingly used clinically for cancer genotyping, but may lead to incidental identification of germline risk alleles. We studied EGFR T790M mutations in non-small cell lung cancer (NSCLC) toward the aim of discriminating germline and cancer-derived variants within cfDNA. EXPERIMENTAL DESIGN: Patients with EGFR-mutant NSCLC, some with known germline EGFR T790M, underwent plasma genotyping. Separately, deidentified genomic data and buffy coat specimens from a clinical plasma next-generation sequencing (NGS) laboratory were reviewed and tested...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28905136/highly-sensitive-detection-of-esr1-mutations-in-cell-free-dna-from-patients-with-metastatic-breast-cancer-using-molecular-barcode-sequencing
#7
Nanae Masunaga, Naofumi Kagara, Daisuke Motooka, Shota Nakamura, Tomohiro Miyake, Tomonori Tanei, Yasuto Naoi, Masafumi Shimoda, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
PURPOSE: We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). METHODS: The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR)...
September 13, 2017: Breast Cancer Research and Treatment
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
#8
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/28683468/correlation-between-circulating-mutant-dna-and-metabolic-tumour-burden-in-advanced-non-small-cell-lung-cancer-patients
#9
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...
August 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28636991/non-invasive-detection-of-somatic-mutations-using-next-generation-sequencing-in-primary-central-nervous-system-lymphoma
#10
Maxime Fontanilles, Florent Marguet, Élodie Bohers, Pierre-Julien Viailly, Sydney Dubois, Philippe Bertrand, Vincent Camus, Sylvain Mareschal, Philippe Ruminy, Catherine Maingonnat, Stéphane Lepretre, Elena-Liana Veresezan, Stéphane Derrey, Hervé Tilly, Jean-Michel Picquenot, Annie Laquerrière, Fabrice Jardin
PURPOSE: Primary central nervous system lymphomas (PCNSL) have recurrent genomic alterations. The main objective of our study was to demonstrate that targeted sequencing of circulating cell-free DNA (cfDNA) released by PCNSL at the time of diagnosis could identify somatic mutations by next-generation sequencing (NGS). PATIENTS AND METHODS: PlasmacfDNA and matched tumor DNA (tDNA) from 25 PCNSL patients were sequenced using an Ion Torrent Personal Genome Machine (Life Technologies®)...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28540249/liquid-biopsies-for-bladder-cancer
#11
EDITORIAL
Douglas G Ward, Richard T Bryan
The development of accurate urinary biomarkers for the non-invasive detection of urothelial bladder cancer (UBC) could transform patient pathways by reducing reliance on cystoscopy, and the identification of highly prognostic (or even predictive) biomarkers could better guide patient management. A number of approaches are being utilised to address these challenges in both urinary- and plasma-borne tumour DNA (tDNA), so-called "liquid biopsies". Next generation sequencing (NGS) and droplet digital PCR (ddPCR) allow detection of very low levels of such tDNA amongst a large excess of non-tumour DNA, the former permitting large mutation panels to be assessed and the latter potentially identifying ultrarare mutant alleles yet restricted for multiplexing...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28536309/development-and-validation-of-an-ultradeep-next-generation-sequencing-assay-for-testing-of-plasma-cell-free-dna-from-patients-with-advanced-cancer
#12
Filip Janku, Shile Zhang, Jill Waters, Li Liu, Helen J Huang, Vivek Subbiah, David S Hong, Daniel D Karp, Siqing Fu, Xuyu Cai, Nishma M Ramzanali, Kiran Madwani, Goran Cabrilo, Debra L Andrews, Yue Zhao, Milind Javle, E Scott Kopetz, Rajyalakshmi Luthra, Hyunsung J Kim, Sante Gnerre, Ravi Vijaya Satya, Han-Yu Chuang, Kristina M Kruglyak, Jonathan Toung, Chen Zhao, Richard Shen, John V Heymach, Funda Meric-Bernstam, Gordon B Mills, Jian-Bing Fan, Neeraj S Salathia
Purpose: Tumor-derived cell-free DNA (cfDNA) in plasma can be used for molecular testing and provide an attractive alternative to tumor tissue. Commonly used PCR-based technologies can test for limited number of alterations at the time. Therefore, novel ultrasensitive technologies capable of testing for a broad spectrum of molecular alterations are needed to further personalized cancer therapy.Experimental Design: We developed a highly sensitive ultradeep next-generation sequencing (NGS) assay using reagents from TruSeqNano library preparation and NexteraRapid Capture target enrichment kits to generate plasma cfDNA sequencing libraries for mutational analysis in 61 cancer-related genes using common bioinformatics tools...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28522829/somatic-tumor-mutations-detected-by-targeted-next-generation-sequencing-in-minute-amounts-of-serum-derived-cell-free-dna
#13
Marjolein J A Weerts, Ronald van Marion, Jean C A Helmijr, Corine M Beaufort, Niels M G Krol, Anita M A C Trapman-Jansen, Winand N M Dinjens, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
The use of blood-circulating cell-free DNA (cfDNA) as 'liquid-biopsy' is explored worldwide, with hopes for its potential in providing prognostic or predictive information in cancer treatment. In exploring cfDNA, valuable repositories are biobanks containing material collected over time, however these retrospective cohorts have restrictive resources. In this study, we aimed to detect tumor-specific mutations in only minute amounts of serum-derived cfDNA by using a targeted next generation sequencing (NGS) approach...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28511612/ngs-analysis-on-tumor-tissue-and-cfdna-for-genotype-directed-therapy-in-metastatic-nsclc-patients-between-hope-and-hype
#14
Alexander T Falk, Simon Heeke, Véronique Hofman, Virginie Lespinet, Camille Ribeyre, Olivier Bordone, Michel Poudenx, Josiane Otto, Georges Garnier, Olivier Castelnau, Joël Guigay, Sylvie Leroy, Charles-Hugo Marquette, Paul Hofman, Marius Ilié
The advent of genomic based precision medicine led to the implementation of biomarker testing in metastatic non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) has been recently implemented to routine diagnostic requirements in lung oncology. Areas covered: Two cases of patients with metastatic NSCLC for whom NGS analysis performed on both tumor and liquid biopsy has not improved the clinical course of their disease are reported. These cases illustrate the difficulty of the so-called 'personalized or precision' medicine in clinical routine practice for metastatic NSCLC...
August 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28506684/study-of-preanalytic-and-analytic-variables-for-clinical-next-generation-sequencing-of-circulating-cell-free-nucleic-acid
#15
Meenakshi Mehrotra, Rajesh R Singh, Wei Chen, Richard S P Huang, Alaa A Almohammedsalim, Bedia A Barkoh, Crystal M Simien, Marcos Hernandez, Carmen Behrens, Keyur P Patel, Mark J Routbort, Russell R Broaddus, L Jeffrey Medeiros, Ignacio I Wistuba, Scott Kopetz, Rajyalakshmi Luthra
Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next-generation sequencing (NGS) has opened up new possibilities for monitoring treatment response and disease progression in patients with solid tumors. However, implementation of cfDNA genotyping in diagnostic laboratories requires systematic assessment of preanalytical parameters and analytical performance of NGS platforms. We assessed the effects of peripheral blood collection tube and plasma separation time on cfDNA yield and integrity and performance of the Ion PGM, Proton, and MiSeq NGS platforms...
May 12, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28502728/technical-validation-of-a-next-generation-sequencing-assay-for-detecting-clinically-relevant-levels-of-breast-cancer-related-single-nucleotide-variants-and-copy-number-variants-using-simulated-cell-free-dna
#16
Xin Yang, Yuxing Chu, Rui Zhang, Yanxi Han, Lucheng Zhang, Yu Fu, Dan Li, Rongxue Peng, Dongdong Li, Jiansheng Ding, Ziyang Li, Meiru Zhao, Kuo Zhang, Tian Lu, Lang Yi, Qisheng Wu, Guigao Lin, Jiehong Xie, Tao Liu, Ling Yang, Xin Yi, Jinming Li
Next-generation sequencing (NGS) is commonly used in a clinical setting for diagnostic and prognostic testing of genetic mutations to select optimal targeted therapies. Herein, we describe the development of a custom NGS assay for detecting single-nucleotide variants (SNVs) and copy number variations (CNVs) in a panel of 51 genes related to breast cancer. We designed and implemented a validation strategy in accordance with principles and guidelines developed by the Next-Generation Sequencing: Standardization of Clinical Testing work group using artificial, cell-free DNA (cfDNA) with mutant fragments prepared in a simple, rapid, and cost-effective manner...
May 11, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28393575/using-circulating-cell-free-dna-to-monitor-personalized-cancer-therapy
#17
REVIEW
Michael Oellerich, Ekkehard Schütz, Julia Beck, Philipp Kanzow, Piers N Plowman, Glen J Weiss, Philip D Walson
High-quality genomic analysis is critical for personalized pharmacotherapy in patients with cancer. Tumor-specific genomic alterations can be identified in cell-free DNA (cfDNA) from patient blood samples and can complement biopsies for real-time molecular monitoring of treatment, detection of recurrence, and tracking resistance. cfDNA can be especially useful when tumor tissue is unavailable or insufficient for testing. For blood-based genomic profiling, next-generation sequencing (NGS) and droplet digital PCR (ddPCR) have been successfully applied...
May 2017: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/28320758/tumor-cell-free-dna-copy-number-instability-predicts-therapeutic-response-to-immunotherapy
#18
Glen J Weiss, Julia Beck, Donald P Braun, Kristen Bornemann-Kolatzki, Heather Barilla, Rhiannon Cubello, Walter Quan, Ashish Sangal, Vivek Khemka, Jordan Waypa, William M Mitchell, Howard Urnovitz, Ekkehard Schütz
Purpose: Chromosomal instability is a fundamental property of cancer, which can be quantified by next-generation sequencing (NGS) from plasma/serum-derived cell-free DNA (cfDNA). We hypothesized that cfDNA could be used as a real-time surrogate for imaging analysis of disease status as a function of response to immunotherapy and as a more reliable tool than tumor biomarkers.Experimental Design: Plasma cfDNA sequences from 56 patients with diverse advanced cancers were prospectively collected and analyzed in a single-blind study for copy number variations, expressed as a quantitative chromosomal number instability (CNI) score versus 126 noncancer controls in a training set of 23 and a blinded validation set of 33...
March 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28229982/circulating-free-dna-mutation-associated-with-response-of-targeted-therapy-in-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer
#19
Qing Ye, Fan Qi, Li Bian, Shao-Hua Zhang, Tao Wang, Ze-Fei Jiang
BACKGROUND: The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA)...
March 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28212557/using-high-sensitivity-sequencing-for-the-detection-of-mutations-in-btk-and-plc%C3%AE-2-genes-in-cellular-and-cell-free-dna-and-correlation-with-progression-in-patients-treated-with-btk-inhibitors
#20
Adam Albitar, Wanlong Ma, Ivan DeDios, Jeffrey Estella, Inhye Ahn, Mohammed Farooqui, Adrian Wiestner, Maher Albitar
Patients with chronic lymphocytic leukemia (CLL) that develop resistance to Bruton tyrosine kinase (BTK) inhibitors are typically positive for mutations in BTK or phospholipase c gamma 2 (PLCγ2). We developed a high sensitivity (HS) assay utilizing wild-type blocking polymerase chain reaction achieved via bridged and locked nucleic acids. We used this high sensitivity assay in combination with Sanger sequencing and next generation sequencing (NGS) and tested cellular DNA and cell-free DNA (cfDNA) from patients with CLL treated with the BTK inhibitor, ibrutinib...
March 14, 2017: Oncotarget
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