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Cell free cancer DNA

Dong-Min Kim, Dong Ho Kim, Woong Jung, Kye Young Lee, Dong-Eun Kim
Mutations in epidermal growth factor receptor (EGFR) are known as biomarkers that cause non-small cell lung cancer. Particularly, approximately 45% of non-small cell lung cancer patients possess a deletion in exon 19 of the EGFR gene. A less invasive method for detecting the EGFR mutation is required; thus, we developed a simple polymerase chain reaction (PCR)-based method for detecting EGFR exon 19 deletion by using a quencher-free fluorescent probe DNA and graphene oxide (GO). In the presence of the exon 19 deletion mutation, the fluorophore-labeled DNA probe was designed to be fully complementary to the mutant sequences...
March 21, 2018: Analyst
David M Barris, Shoshana B Weiner, Robert A Dubin, Michael Fremed, Xusheng Zhang, Sajida Piperdi, Wendong Zhang, Shahina Maqbool, Jonathan Gill, Michael Roth, Bang Hoang, David Geller, Richard Gorlick, Daniel A Weiser
Identification and quantification of somatic alterations in plasma-derived, circulating tumor DNA (ctDNA) is gaining traction as a non-invasive and cost effective method of disease monitoring in cancer patients, particularly to evaluate response to treatment and monitor for disease recurrence. To our knowledge, genetic analysis of ctDNA in osteosarcoma has not yet been studied. To determine whether somatic alterations can be detected in ctDNA and perhaps applied to patient management in this disease, we collected germline, tumor, and serial plasma samples from pediatric, adolescent, and young adult patients with osteosarcoma and used targeted Next Generation Sequencing (NGS) to identify somatic single nucleotide variants (SNV), insertions and deletions (INDELS), and structural variants (SV) in 7 genes commonly mutated in osteosarcoma...
February 27, 2018: Oncotarget
Anna Babayan, Klaus Pantel
Progress in sensitive analytical approaches has opened new avenues for the detection of cells or products such as circulating cell-free DNA released by tumors. These 'liquid biopsies' are being explored in clinical trials for early cancer detection, prediction of recurrent disease, and assessment of therapeutic resistance mechanisms.
March 20, 2018: Genome Medicine
Ningyu Huang, Wenbo Lin, Xiuyu Shi, Tao Tao
AIM: To explore the independent prognostic value of STK24 expression in terms of overall survival and recurrence-free survival and the potential mechanisms of its dysregulation in non-small-cell lung adenocarcinoma. PATIENTS & METHODS: Data were from the Cancer Genome Atlas-lung adenocarcinoma. RESULTS: Increased STK24 expression was an independent prognostic indicator of unfavorable overall survival (Hazard ratio: 1.478; 95% CI: 1.149-1...
March 20, 2018: Future Oncology
Ding Qian-Shan, Zhang Li, Wang Bi-Cheng, Zeng Zhi, Zou Xian-Qiong, Cao Peng-Bo, M S Zhou Guang-Ming, Tang Meng, Wu Lu, B S Wu Lian-Lian, Yu Hong-Gang, Guo Yong, Zhou Fu-Xiang
Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types employing immunohistochemical staining and analysis of mRNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, oesophagus and bladder)...
March 16, 2018: Human Pathology
Alejandro D Bolzán, Martha S Bianchi
Bleomycin (BLM) is an antibiotic isolated from Streptomyces verticillus. It has radiomimetic actions on DNA thus it has been widely used in clinical chemotherapy for the treatment of different types of cancer, including head and neck tumors, lymphomas, squamous-cell carcinomas and germ-cell tumors. Because of this, the study of BLM genotoxicity is of practical interest. This antibiotic is an S-independent clastogen and an agent that generates free radicals and induces single- and double-strand breaks in DNA...
January 2018: Mutation Research
Kathryn J Gray, Louise E Wilkins-Haug
Prenatal aneuploidy screening changed significantly in 2012 when cell-free fetal deoxyribonucleic acid (DNA) was introduced as a noninvasive prenatal test. A noninvasive prenatal test detects cell free fragments of fetal DNA from the placenta circulating in maternal blood that coexist with cell-free DNA (cfDNA) of maternal origin. Using next-generation sequencing, the noninvasive prenatal test compares maternal and fetal cfDNA ratios for chromosomes of interest (i.e., 21, 18, 13, X, and Y) to assess chromosomal aneuploidy...
April 2018: Pediatric Radiology
Davina Gale, Andrew R J Lawson, Karen Howarth, Mikidache Madi, Bradley Durham, Sarah Smalley, John Calaway, Shannon Blais, Greg Jones, James Clark, Peter Dimitrov, Michelle Pugh, Samuel Woodhouse, Michael Epstein, Ana Fernandez-Gonzalez, Alexandra S Whale, Jim F Huggett, Carole A Foy, Gerwyn M Jones, Hadas Raveh-Amit, Karin Schmitt, Alison Devonshire, Emma Green, Tim Forshew, Vincent Plagnol, Nitzan Rosenfeld
INTRODUCTION: Detection and monitoring of circulating tumor DNA (ctDNA) is rapidly becoming a diagnostic, prognostic and predictive tool in cancer patient care. A growing number of gene targets have been identified as diagnostic or actionable, requiring the development of reliable technology that provides analysis of multiple genes in parallel. We have developed the InVision™ liquid biopsy platform which utilizes enhanced TAm-Seq™ (eTAm-Seq™) technology, an amplicon-based next generation sequencing method for the identification of clinically-relevant somatic alterations at low frequency in ctDNA across a panel of 35 cancer-related genes...
2018: PloS One
Qingwang Xue, Chunxue Liu, Xia Li, Li Dai, Huaisheng Wang
Various fluorescent sensing systems for miRNAs detection have been developed. But they mostly contain enzymatic amplification reactions and label procedures. The strict reaction conditions of tool enzymes and the high cost of labeling limit their potential applications, especially in complex biological matrix. Here we have addressed the difficult problems and report a strategy for label-free fluorescent DNA dendrimers based on enzyme-free nonlinear hybridization chain reaction (HCR)-mediated multiple G-quadruplex for simple, sensitive and selective detection of miRNAs with low-background signal...
March 16, 2018: Bioconjugate Chemistry
Vincent Plagnol, Samuel Woodhouse, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank de Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Clive Morris, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones, Tim Forshew
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA...
2018: PloS One
Antonio Fadda, Davide Gentilini, Loredana Moi, Ludovic Barault, Vera Piera Leoni, Pia Sulas, Luigi Zorcolo, Angelo Restivo, Francesco Cabras, Federica Fortunato, Cesare Zavattari, Liliana Varesco, Viviana Gismondi, Maria Rosaria De Miglio, Antonio Mario Scanu, Federica Colombi, Pasquale Lombardi, Ivana Sarotto, Eleonora Loi, Francesco Leone, Silvia Giordano, Federica Di Nicolantonio, Amedeo Columbano, Patrizia Zavattari
Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment...
March 15, 2018: International Journal of Cancer. Journal International du Cancer
Kristina M Jordahl, Timothy W Randolph, Xiaoling Song, Cassandra L Sather, Lesley F Tinker, Amanda I Phipps, Karl T Kelsey, Emily White, Parveen Bhatti
BACKGROUND: Differential DNA methylation as measured in blood is a promising marker of bladder cancer susceptibility. However, previous studies have exclusively used post-diagnostic blood samples, meaning that observed associations may be markers of disease rather than susceptibility. METHODS: Genome-wide methylation was measured in pre-diagnostic blood samples, using the Illumina Infinium HumanMethylation450 Bead Array, among 440 bladder cancer cases with the transitional cell carcinoma (TCC) subtype and 440 matched cancer-free controls from the Women's Health Initiative (WHI) cohort...
March 14, 2018: Cancer Epidemiology, Biomarkers & Prevention
Xiaohan Chen, Golbarg M Roozbahani, Zijing Ye, Youwen Zhang, Rui Ma, Jialing Xiang, Xiyun Guan
Cancers are caused by mutations to genes that regulate cell normal functions. The capability to rapid and reliable detection of specific target gene variations can facilitate early disease detection and diagnosis, and also enables personalized treatment of cancer. Most of the currently available methods for DNA mutation detection are time-consuming and/or require the use of labels or sophisticated instruments. In this work, we reported a label-free enzymatic reaction-based nanopore sensing strategy to detect DNA mutations, including base substitution, deletion, and insertion...
March 14, 2018: ACS Applied Materials & Interfaces
Jun Li, Renzhong Liu, Cuihong Huang, Shifu Chen, Mingyan Xu
Cell-free tumor DNA (ctDNA) is a kind of potential tumor biomarkers originated from cancer lesion in the circulating liquids. Liquid biopsy, as a minimally invasive or noninvasive manner, is a cutting-edge technology to detect ctDNA and other circulating biomarkers in the blood or other body fluids. ctDNA is mostly used for cancer patients to select targeted drugs in clinical application. In addition, ctDNA could also be applied to monitor tumor progression and recurrence. In conclusion, ctDNA is a very promising tumor biomarker for diagnosis and monitoring, which would increasingly become a routine clinical application in recent years...
2018: Methods in Molecular Biology
Nicholas C Eastley, Barbara Ottolini, Rita Neumann, Jin-Li Luo, Robert K Hastings, Imran Khan, David A Moore, Claire P Esler, Jacqueline A Shaw, Nicola J Royle, Robert U Ashford
Following treatment 40% of soft tissue sarcoma (STS) patients suffer disease recurrence. In certain cancers circulating cell free DNA (cfDNA) and circulating tumour-derived DNA (ctDNA) characteristics correlate closely with disease burden, making them exciting potential sources of biomarkers. Despite this, the circulating nucleic acid characteristics of only 2 STS patients have been reported to date. To address this we used an Ion AmpliSeq™ panel custom specifically designed for STS patients to conduct a genetic characterisation of plasma cfDNA, buffy coat (germline) DNA and where available Formalin-Fixed Paraffin-Embedded (FFPE) primary STS tissue DNA in a cohort of 11 metastatic STS patients...
February 13, 2018: Oncotarget
Meenakshi Mehrotra, Rajesh R Singh, Sanam Loghavi, Dzifa Yawa Duose, Bedia A Barkoh, Carmen Behrens, Keyur P Patel, Mark J Routbort, Scott Kopetz, Russell R Broaddus, L Jeffrey Medeiros, Ignacio I Wistuba, Rajyalakshmi Luthra
A suitable clinical-grade platform is required for detection of somatic mutations with high sensitivity in cell-free DNA (cfDNA) of patients with solid tumors. In this study, we evaluated in parallel ultra-deep NGS with MassARRAY and allele-specific droplet digital PCR (ddPCR) for cfDNA genotyping and correlated cfDNA yield and mutation status with overall survival (OS) of patients. We assessed plasma samples from 46 patients with various advanced metastatic solid tumors and known mutations by deep sequencing using an Ampliseq cancer hotspot panel V2 on Ion Proton...
February 13, 2018: Oncotarget
Louise Rasmussen, Ib Jarle Christensen, Marielle Herzog, Jake Micallef, Hans Jørgen Nielsen
The aim was to evaluate serum levels of circulating cell-free nucleosomes (ccfn) containing a variety of epigenetic signals including 5-methylcytosine DNA, histone modifications H3K9Me3, H3K9Ac, H3S10PO4, H3K36Me3, H4K20Me3, H4PanAc and pH2AX, nucleosome variant H2AZ and nucleosome adducts with HMGB1 and EZH2 as well as ccfn per se, in addition to develop and evaluate predictor models based on the above mentioned ccfn and including serum levels of carcinoembryonic antigen (CEA), in early detection of colorectal cancer (CRC)...
February 13, 2018: Oncotarget
Elena Castellanos-Rizaldos, Dominik G Grimm, Vasisht Tadigotla, James Hurley, John Healy, Patricia L Neal, Mia Sher, Raajdeep Venkatesan, Chris Karlovich, Mitch Raponi, Anne K Krug, Mikkel Noerholm, Jihane Tannous, Bakhos A Tannous, Luis E Raez, Johan Skog
PURPOSE: About 60% of non-small cell lung cancer (NSCLC) patients develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy through the EGFR T790M mutation. Patients with this mutation respond well to third generation tyrosine kinase inhibitors, but obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Liquid biopsies using circulating free tumor DNA (cfDNA) have emerged as a non-invasive option to detect the mutation, however sensitivity is low as many patients have too few detectable copies in circulation...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Laura Lupini, Anna Moretti, Cristian Bassi, Alessio Schirone, Massimo Pedriali, Patrizia Querzoli, Roberta Roncarati, Antonio Frassoldati, Massimo Negrini
Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms. Here, we developed a high sensitivity approach based on enhanced-ice-COLD-PCR for detecting ESR1 mutations. The method produced an enrichment up to 100-fold and allowed the unambiguous detection of ESR1 mutations even when they consisted of only 0...
March 12, 2018: Scientific Reports
Jessica G Rushton, Reinhard Ertl, Dieter Klein, Alexander Tichy, Barbara Nell
Objectives Feline diffuse iris melanoma (FDIM) is the most common malignant primary intraocular tumour in cats, with reported metastases rates between 19% and 63%. Currently, the only available diagnostic tool for a tentative diagnosis is histopathological examination of the enucleated eye. Therefore, the veterinary ophthalmologist is often faced with the dilemma of whether to enucleate an oftentimes visual eye or to continue monitoring, with the risk of metastases developing. In the past, cell-free DNA (cfDNA) gained more attention in human medicine, especially in the field of oncology...
March 1, 2018: Journal of Feline Medicine and Surgery
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