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Cell free circulating cancer DNA

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https://www.readbyqxmd.com/read/28940814/preanalytical-blood-sample-workup-for-cell-free-dna-analysis-using-droplet-digital-pcr-for-future-molecular-cancer-diagnostics
#1
Joost H van Ginkel, Daan A van den Broek, Joyce van Kuik, Dorothé Linders, Roel de Weger, Stefan M Willems, Manon M H Huibers
In current molecular cancer diagnostics, using blood samples of cancer patients for the detection of genetic alterations in plasma (cell-free) circulating tumor DNA (ctDNA) is an emerging practice. Since ctDNA levels in blood are low, highly sensitive Droplet Digital PCR (ddPCR) can be used for detecting rare mutational targets. In order to perform ddPCR on blood samples, a standardized procedure for processing and analyzing blood samples is necessary to facilitate implementation into clinical practice. Therefore, we assessed the technical sample workup procedure for ddPCR on blood plasma samples...
September 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28937589/viral-cellular-dna-junctions-as-molecular-markers-for-assessing-intra-tumor-heterogeneity-in-cervical-cancer-and-for-the-detection-of-circulating-tumor-dna
#2
Katrin Carow, Mandy Gölitz, Maria Wolf, Norman Häfner, Lars Jansen, Heike Hoyer, Elisabeth Schwarz, Ingo B Runnebaum, Matthias Dürst
The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV) DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity. Moreover, we assessed the potential of these fragments as molecular tumor markers and analyzed their suitability for the detection of circulating tumor DNA in sera of cervical cancer patients...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#3
Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian, Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals...
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28915599/copy-number-variations-of-circulating-cell-free-dna-in-urothelial-carcinoma-of-the-bladder-patients-treated-with-radical-cystectomy-a-prospective-study
#4
Armin Soave, Felix K-H Chun, Timo Hillebrand, Michael Rink, Lars Weisbach, Bettina Steinbach, Margit Fisch, Klaus Pantel, Heidi Schwarzenbach
The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911086/large-scale-prospective-screening-of-egfr-mutations-in-the-blood-of-advanced-nsclc-patients-to-guide-treatment-decisions
#5
C Mayo-de-Las-Casas, N Jordana-Ariza, M Garzón-Ibañez, A Balada-Bel, J Bertrán-Alamillo, S Viteri-Ramírez, N Reguart, M A Muñoz-Quintana, P Lianes-Barragan, C Camps, E Jantús, J Remon-Massip, S Calabuig, D Aguiar, M L Gil, N Viñolas, A K Santos-Rodríguez, M Majem, B García-Peláez, S Villatoro, A Pérez-Rosado, J C Monasterio, E Ovalle, M J Catalán, R Campos, D Morales-Espinosa, A Martínez-Bueno, M González-Cao, X González, I Moya-Horno, A E Sosa, N Karachaliou, R Rosell, M A Molina-Vila
Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28911069/clinical-utility-of-circulating-dna-analysis-for-rapid-detection-of-actionable-mutations-to-select-metastatic-colorectal-patients-for-anti-egfr-treatment
#6
A R Thierry, S El Messaoudi, C Mollevi, J L Raoul, R Guimbaud, D Pezet, P Artru, E Assenat, C Borg, M Mathonnet, C De La Fouchardière, O Bouché, C Gavoille, C Fiess, B Auzemery, R Meddeb, E Lopez-Crapez, C Sanchez, B Pastor, M Ychou
Background: While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods: Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients)...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28903362/cell-free-circulating-dna-integrity-is-an-independent-predictor-of-impending-breast-cancer-recurrence
#7
Jie Cheng, Katarina Cuk, Jörg Heil, Michael Golatta, Sarah Schott, Christof Sohn, Andreas Schneeweiss, Barbara Burwinkel, Harald Surowy
Non-invasive blood-based molecule markers are evaluated as promising biomarkers these days. Here we investigated the potential of cell-free circulating DNA Integrity (cfDI) as blood-based marker for the prediction of recurrence during the follow-up of breast cancer patients within a prospective study cohort. cfDI was determined in plasma of 212 individuals, by measuring ALU and LINE1 repetitive DNA elements using quantitative PCR. A significant decrease of cfDI in recurrent breast cancer patients was observed...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899967/circulating-cell-free-dna-for-metastatic-cervical-cancer-detection-genotyping-and-monitoring
#8
Zhigang Kang, Sanja Stevanović, Christian S Hinrichs, Liang Cao
PURPOSE: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making. PATIENTS AND METHODS: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet (dd) PCR...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28890826/mutational-burden-on-circulating-cell-free-tumor-dna-testing-as-a-surrogate-marker-of-mismatch-repair-deficiency-or-microsatellite-instability-in-patients-with-colorectal-cancers
#9
Pashtoon Murtaza Kasi
No abstract text is available yet for this article.
August 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28889390/dna-methylation-analysis-from-body-fluids
#10
Dimo Dietrich
Circulating cell-free DNA (ccfDNA) can be found in various body fluids, i.e., blood (serum and plasma), urine, pleural effusions, and ascites. While ccfDNA predominantly originates from physiological processes, a fraction might be related to pathological events, e.g., cancer. Aberrant DNA methylation, which is considered a hallmark of cancer, can be assessed accurately in ccfDNA. Consequently, DNA methylation testing in body fluids represents a powerful diagnostic tool in the clinical management of malignant diseases...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28884371/egfr-t790m-mutation-testing-of-non-small-cell-lung-cancer-tissue-and-blood-samples-artificially-spiked-with-circulating-cell-free-tumor-dna-results-of-a-round-robin-trial
#11
Jana Fassunke, Michaela Angelika Ihle, Dido Lenze, Annika Lehmann, Michael Hummel, Claudia Vollbrecht, Roland Penzel, Anna-Lena Volckmar, Albrecht Stenzinger, Volker Endris, Andreas Jung, Ulrich Lehmann, Silke Zeugner, Gustavo Baretton, Hans Kreipe, Peter Schirmacher, Thomas Kirchner, Manfred Dietel, Reinhard Büttner, Sabine Merkelbach-Bruse
The European Commision (EC) recently approved osimertinib for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR T790M mutations. Besides tissue-based testing, blood samples containing cell-free circulating tumor DNA (ctDNA) can be used to interrogate T790M status. Herein, we describe the conditions and results of a round robin trial (RRT) for T790M mutation testing in NSCLC tissue specimens and peripheral blood samples spiked with cell line DNA mimicking tumor-derived ctDNA...
September 8, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28881655/dna-hypomethylation-of-cbs-promoter-induced-by-folate-deficiency-is-a-potential-noninvasive-circulating-biomarker-for-colorectal-adenocarcinomas
#12
Geng Xue, Chao-Jing Lu, Shu-Jun Pan, Yin-Ling Zhang, Hui Miao, Shi Shan, Xiao-Ting Zhu, Yi Zhang
Aberrant DNA methylation patterns, which induced by folate deficiency, play important roles in tumorigenesis of colorectal cancer (CRC). Some DNA methylation alterations can also be detected in cell-free DNA (cfDNA) of patients' plasma, making cfDNA an ideal noninvasive circulating biomarker. However, exact DNA methylation alterations induced by folate deficiency in tumorigenesis of CRC and exact potential circulating cfDNA methylation biomarker are still unclear. Therefore, DNA methylation patterns of the normal human colon mucosal epithelial cell line (NCM460), cultured with normal or low folate content, were screened and the DNA hypomethylation of cystathionine-beta-synthase (CBS) promoter was further validated in vitro and vivo...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28868131/circulating-tumor-cells-silent-predictors-of-metastasis
#13
REVIEW
LanLan Zhou, David T Dicker, Elizabeth Matthew, Wafik S El-Deiry, R Katherine Alpaugh
Circulating tumor cells (CTCs) were added to the arsenal of clinical testing in 2004 for three cancer types: metastatic breast, prostate, and colorectal cancer. CTCs were found to be an independent prognostic indicator of survival for these three diseases. Multiple enrichment/isolation strategies have been developed and numerous assay applications have been performed using both single and pooled captured/enriched CTCs. We have reviewed the isolation techniques and touched on many analyses. The true utility of a CTC is that it acts as a "silent" predictor of metastatic disease...
2017: F1000Research
https://www.readbyqxmd.com/read/28864639/reversion-mutations-with-clinical-use-of-parp-inhibitors-many-genes-many-versions
#14
Susan M Domchek
Reversion mutations associated with PARP inhibitor resistance have been identified in tumors with RAD51C, RAD51D, and PALB2 as well as BRCA1 and BRCA2 mutations. Multiple different reversion mutations can occur in a single patient, and they can be detected by analysis of circulating cell-free DNA. Cancer Discov; 7(9); 937-9. ©2017 AACRSee related article by Kondrashova et al., p. 984See related article by Quigley et al., p. 999See related article by Goodall et al., p. 1006.
September 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28854070/first-in-human-phase-i-study-of-the-tamoxifen-metabolite-z-endoxifen-in-women-with-endocrine-refractory-metastatic-breast-cancer
#15
Matthew P Goetz, Vera J Suman, Joel M Reid, Don W Northfelt, Michael A Mahr, Andrew T Ralya, Mary Kuffel, Sarah A Buhrow, Stephanie L Safgren, Renee M McGovern, John Black, Travis Dockter, Tufia Haddad, Charles Erlichman, Alex A Adjei, Dan Visscher, Zachary R Chalmers, Garrett Frampton, Benjamin R Kipp, Minetta C Liu, John R Hawse, James H Doroshow, Jerry M Collins, Howard Streicher, Matthew M Ames, James N Ingle
Purpose Endoxifen is a tamoxifen metabolite with potent antiestrogenic activity. Patients and Methods We performed a phase I study of oral Z-endoxifen to determine its toxicities, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity. Eligibility included endocrine-refractory, estrogen receptor-positive metastatic breast cancer. An accelerated titration schedule was applied until moderate or dose-limiting toxicity occurred, followed by a 3+3 design and expansion at 40, 80, and 100 mg per day...
August 30, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28845132/cell-free-dna-in-non-small-cell-lung-cancer
#16
Vaida Gedvilaitė, Diana Schveigert, Saulius Cicėnas
Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). Advances in the knowledge of the biology of non-small cell lung cancer have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients' overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic...
2017: Acta medica Lituanica
https://www.readbyqxmd.com/read/28841389/osimertinib-as-first-line-treatment-of-egfr-mutation-positive-advanced-non-small-cell-lung-cancer
#17
Suresh S Ramalingam, James C-H Yang, Chee Khoon Lee, Takayasu Kurata, Dong-Wan Kim, Thomas John, Naoyuki Nogami, Yuichiro Ohe, Helen Mann, Yuri Rukazenkov, Serban Ghiorghiu, Daniel Stetson, Aleksandra Markovets, J Carl Barrett, Kenneth S Thress, Pasi A Jänne
Purpose The Osimertinib First Time in Patients Ascending Dose (AURA) study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naïve patients to examine clinical activity and safety of osimertinib (an epidermal growth factor receptor [EGFR] -tyrosine kinase inhibitor selective for EGFR-tyrosine kinase inhibitor sensitizing [ EGFRm] and EGFR T790M resistance mutations) as first-line treatment of EGFR-mutated advanced non-small-cell lung cancer (NSCLC). Patients and Methods Sixty treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily (30 patients per cohort)...
August 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28838384/cell-free-circulating-tumor-dna-supplementing-tissue-biopsies-for-identification-of-targetable-mutations-implications-for-precision-medicine-and-considerations-for-reconciling-results
#18
J Kevin Hicks, James Saller, Emilie Wang, Theresa Boyle, Jhanelle E Gray
Cell-free circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is emerging as a noninvasive technique for detecting targetable mutations. We describe two lung adenocarcinoma cases that show the clinical utility of supplementing tumor biopsy molecular interrogation with ctDNA NGS. For both cases, ctDNA NGS identified actionable mutations that were previously not reported by molecular interrogation of tissue. Explanations are provided for the observed differences between ctDNA and tumor biopsy genomic results along with considerations for reconciling findings...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28830871/cell-free-circulating-dna-integrity-based-on-peripheral-blood-as-a-biomarker-for-diagnosis-of-cancer-a-systematic-review
#19
Jie Cheng, Qiuqiong Tang, Xue Cao, Barbara Burwinkel
BACKGROUND: Cell-free DNA integrity (cfDI) has been identified as a potential diagnostic biomarker for different types of cancer as the importance of liquid biopsy. METHODS: This systematic review aims to assess the diagnostic performance of cfDI in cancer. After an extensive literature search until 28th February, 2017, 25 articles including 40 studies were included. The description of all the studies was analyzed. The sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios, weighted symmetric summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) of cfDI in these studies were calculated...
August 22, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28829813/clinical-validation-of-a-highly-sensitive-assay-to-detect-egfr-mutations-in-plasma-cell-free-dna-from-patients-with-advanced-lung-adenocarcinoma
#20
Yuping Li, Hanyan Xu, Shanshan Su, Junru Ye, Junjie Chen, Xuru Jin, Quan Lin, Dongqing Zhang, Caier Ye, Chengshui Chen
BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive epidermal growth factor receptor (EGFR) mutations detection in lung cancer patients, but the existing methods have limitations in sensitivity or in availability. In this study, we evaluated the performance of a novel assay called ADx-SuperARMS in detecting EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma. METHODS: A total of 109 patients with metastatic advanced adenocarcinoma were recruited who provided both blood samples and matched tumor tissue samples...
2017: PloS One
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