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circulating tumour DNA

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
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
Niven Mehra, David Dolling, Semini Sumanasuriya, Rossitza Christova, Lorna Pope, Suzanne Carreira, George Seed, Wei Yuan, Jane Goodall, Emma Hall, Penny Flohr, Gunther Boysen, Diletta Bianchini, Oliver Sartor, Mario A Eisenberger, Karim Fizazi, Stephane Oudard, Mustapha Chadjaa, Sandrine Macé, Johann S de Bono
BACKGROUND: Noninvasive biomarkers are needed to guide metastatic castration-resistant prostate cancer (mCRPC) treatment. OBJECTIVE: To clinically qualify baseline and on-treatment cell-free DNA (cfDNA) concentrations as biomarkers of patient outcome following taxane chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Blood for cfDNA analyses was prospectively collected from 571 mCRPC patients participating in two phase III clinical trials, FIRSTANA (NCT01308567) and PROSELICA (NCT01308580)...
February 27, 2018: European Urology
Maria Gonzalez-Cao, Clara Mayo de Las Casas, Nuria Jordana Ariza, Jose L Manzano, Miguel Á Molina-Vila, Virtudes Soriano, Teresa Puertolas, Ariadna Balada, Ainara Soria, Margarita Majem, Clara Montagut, Eva Muñoz, Delvys Rodriguez-Abreu, Elisabeth Perez, Almudena Garcia, Javier Cortes, Ana Drozdowskyj, Niki Karachaliou, Rafael Rosell
Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome...
February 23, 2018: Melanoma Research
Perumal Jayaraj, Seema Sen, Srishti Rangarajan, Neelanjana Ray, Kirtana Vasu, Vijay Kumar Singh, Rajendra Phartyal, Sarika Yadav, Anita Verma
BACKGROUND: p53 is a stress-activated tumour suppressor gene, and its mutation has been associated with solid tumours including non-melanoma skin cancers. Sestrin2 expression is associated with DNA damage and oxidative stress and has been described as a downstream target of p53 network. However, its role in sebaceous gland carcinoma (SGC) remains unexplored. OBJECTIVES: To determine the role of p53 and its downstream target gene sestrin2 expression and p53 gene mutation status in SGC...
February 24, 2018: British Journal of Ophthalmology
Yoshitaka Seki, Yutaka Fujiwara, Takashi Kohno, Kazushi Yoshida, Yasushi Goto, Hidehito Horinouchi, Shintaro Kanda, Hiroshi Nokihara, Noboru Yamamoto, Kazuyoshi Kuwano, Yuichiro Ohe
No abstract text is available yet for this article.
2018: ESMO Open
Shelize Khakoo, Alexandros Georgiou, Marco Gerlinger, David Cunningham, Naureen Starling
Circulating cell free tumour DNA (ctDNA) maintains the same genomic alterations that are present in the corresponding tumour, thereby allowing for quantitative and qualitative real-time evaluation in body fluids as an alternative to onerous repeat biopsies. Improvements in the sensitivity of techniques used to identify ctDNA has led to a surge of research investigating its role in the detection of: early disease, relapse, response to therapy and emerging drug resistance mechanisms. Following curative surgery, ctDNA detection is a promising marker of minimal residual disease and could better select patients for adjuvant chemotherapy...
February 2018: Critical Reviews in Oncology/hematology
Andrew E Rodda, Bradyn J Parker, Andrew Spencer, Simon R Corrie
Liquid biopsies that analyze circulating tumor DNA (ctDNA) hold great promise in the guidance of clinical treatment for various cancers. However, the innate characteristics of ctDNA make it a difficult target: ctDNA is highly fragmented, and found at very low concentrations, both in absolute terms and relative to wildtype species. Clinically relevant target sequences often differ from the wildtype species by a single DNA base pair. These characteristics make analyzing mutant ctDNA a uniquely difficult process...
February 23, 2018: ACS Sensors
Kezhong Chen, Heng Zhao, Fan Yang, Bengang Hui, Tianyang Wang, Lieu Tu Wang, Yanbin Shi, Jun Wang
INTRODUCTION: Circulating tumour DNA (ctDNA) has potential applications in cancer management. Most previous studies about ctDNA focused on advanced stage cancer patients. We have completed a clinical prospective study (NCT02645318) and showed the feasibility and clinical application of ctDNA detection in early stage non-small cell lung cancer (NSCLC) patients. The aim of this study is to investigate the elimination rate of ctDNA level after surgery. This is the first prospective study to evaluate the perioperative dynamic changes of ctDNA in surgical lung cancer patients...
February 6, 2018: BMJ Open
Jeanne Tie, Joshua D Cohen, Yuxuan Wang, Lu Li, Michael Christie, Koen Simons, Hany Elsaleh, Suzanne Kosmider, Rachel Wong, Desmond Yip, Margaret Lee, Ben Tran, David Rangiah, Matthew Burge, David Goldstein, Madhu Singh, Iain Skinner, Ian Faragher, Matthew Croxford, Carolyn Bampton, Andrew Haydon, Ian T Jones, Christos S Karapetis, Timothy Price, Mary J Schaefer, Jeanne Ptak, Lisa Dobbyn, Natallie Silliman, Isaac Kinde, Cristian Tomasetti, Nickolas Papadopoulos, Kenneth Kinzler, Bert Volgestein, Peter Gibbs
OBJECTIVE: For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC. DESIGN: We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery...
February 2, 2018: Gut
Barbara Kinga Barták, Zsófia Brigitta Nagy, Sándor Spisák, Zsolt Tulassay, Magdolna Dank, Péter Igaz, Béla Molnár
INTRODUCTION: Cell-free DNA (cfDNA) was first detected in human plasma in the 1940s, but the knowledge on its regulation and rate of release is incomplete. CfDNA can originate from both normal and tumour cells. AIM: Our aims were to investigate the rate of cfDNA's release in SHO mice/HT-29 colorectal adenocarcinoma cell line xenograft model and to define the decay of methylated and non-methylated DNA fragments in C57BL/6 bloodstream. METHOD: SHO mice were xenografted with human HT-29 cells, than blood samples were collected over 2 months...
February 2018: Orvosi Hetilap
Caitlin M Stewart, Prachi D Kothari, Florent Mouliere, Richard Mair, Saira Somnay, Ryma Benayed, Ahmet Zehir, Britta Weigelt, Sarah-Jane Dawson, Maria E Arcila, Michael F Berger, Dana Wy Tsui
Over the past decade, advances in molecular biology and genomics techniques have revolutionized the diagnosis and treatment of cancer. The technological advances in tissue profiling have also been applied to the study of cell-free nucleic acids, an area of increasing interest for molecular pathology. Cell-free nucleic acids are released from tumour cells into the surrounding body fluids and can be assayed non-invasively. The repertoire of genomic alterations in circulating tumour DNA (ctDNA) is reflective of primary tumours as well as distant metastatic sites and can be sampled multiple times, thereby overcoming the limitations of the analysis of single biopsies...
January 30, 2018: Journal of Pathology
Francesco Sclafani, Ian Chau, David Cunningham, Jens C Hahne, George Vlachogiannis, Zakaria Eltahir, Andrea Lampis, Chiara Braconi, Eleftheria Kalaitzaki, David Gonzalez De Castro, Andrew Wotherspoon, Jaume Capdevila, Bengt Glimelius, Noelia Tarazona, Ruwaida Begum, Hazel Lote, Sanna Hulkki Wilson, Giulia Mentrasti, Gina Brown, Diana Tait, Jacqueline Oates, Nicola Valeri
There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue...
January 23, 2018: Scientific Reports
Peter Celec, Barbora Vlková, Lucia Lauková, Janka Bábíčková, Peter Boor
Cell-free DNA (cfDNA) is present in various body fluids and originates mostly from blood cells. In specific conditions, circulating cfDNA might be derived from tumours, donor organs after transplantation or from the foetus during pregnancy. The analysis of cfDNA is mainly used for genetic analyses of the source tissue -tumour, foetus or for the early detection of graft rejection. It might serve also as a nonspecific biomarker of tissue damage in critical care medicine. In kidney diseases, cfDNA increases during haemodialysis and indicates cell damage...
January 18, 2018: Expert Reviews in Molecular Medicine
O Nordgård, K Tjensvoll, B Gilje, K Søreide
BACKGROUND: Blood is the most extensively studied body fluid and, because it contains circulating tumour cells (CTCs) and circulating tumour-derived cell-free DNA (ctDNA), it may represent a liquid biopsy for cancer. Methods for enrichment and detection of CTCs and ctDNA, their clinical applications and future opportunities in gastrointestinal cancers were the focus of this review. METHODS: The PubMed database was searched for literature up to 24 June 2017, with a focus on the past 10 years...
January 2018: British Journal of Surgery
Jacques Raphael, Danielle Desautels, Kathleen I Pritchard, Ekaterina Petkova, Prakeshkumar S Shah
Phosphoinositide 3-kinase (PI3K) inhibitors may overcome drug resistance and improve advanced breast cancer (ABC) outcomes. We conducted a systematic review and meta-analysis to assess the efficacy and safety of adding a PI3K inhibitor to the standard of care (SOC) treatment in ABC. The electronic databases Ovid, PubMed, Cochrane Central Register of Controlled Trials and Embase, were searched for relevant randomised trials. Pooled hazard ratios (HRs) for progression-free survival (PFS) and pooled risk ratios (RRs) for objective response rates (ORRs), disease control rates (DCRs) and toxicity were meta-analysed using the Mantel-Haenszel method and generic inverse variance...
January 10, 2018: European Journal of Cancer
Helen Mann, Frank Andersohn, Carolyn Bodnar, Tetsuya Mitsudomi, Tony S K Mok, James Chih-Hsin Yang, Christopher Hoyle
BACKGROUND AND OBJECTIVE: An adjusted indirect comparison was conducted to assess efficacy outcomes, particularly overall survival (OS), of osimertinib versus platinum-based doublet chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) T790M mutation-positive non-small-cell lung cancer (NSCLC) who had progressed following an EGFR tyrosine kinase inhibitor (TKI). Analysis of treatment effect from two separate trials had the potential to more accurately estimate the magnitude of OS benefit due to absence of confounding due to treatment switching from the control arm to the osimertinib arm of the ongoing randomized control trial, AURA3...
December 15, 2017: Clinical Drug Investigation
Sridurga Mithraprabhu, Andrew Spencer
No abstract text is available yet for this article.
October 31, 2017: Oncotarget
Haixing Wang, Beifang Li, Zhentao Liu, Jifang Gong, Lin Shao, Jun Ren, Yunyun Niu, Shiping Bo, Zhongwu Li, Yumei Lai, Sijia Lu, Jing Gao, Lin Shen
BACKGROUND: HER2 status is significant to trastuzumab therapy; however, it is difficult to determine HER2 status accurately with few pieces of biopsies from advanced gastric cancer (AGC) due to highly heterogeneity and invasive behaviour, which will be investigated in this study. METHODS: Fifty-six patients with AGC were included in this study. Primary tumour tissues and matched plasmas before medication from 36 patients were retrospectively collected, and the other 20 patients with primary tumour tissues and paired plasmas were prospectively collected...
January 2018: European Journal of Cancer
Nidal Muhanna, Marco A Di Grappa, Harley H L Chan, Tahsin Khan, Cheng S Jin, Yangqiao Zheng, Jonathan C Irish, Scott V Bratman
In cancer patients, circulating tumour-derived DNA (ctDNA) levels imperfectly reflect disease burden apparent on medical imaging. Further evaluation of ctDNA levels over time is needed to better understand the correlation with tumour growth and therapeutic response. We describe ctDNA kinetics within an orthotopic, immunocompetent preclinical rabbit model of local-regionally advanced head and neck squamous cell carcinoma (HNSCC). Monitoring primary tumour and metastatic lymph node volume by computed tomography (CT), we observed a correlation between ctDNA levels and tumour burden...
December 1, 2017: Scientific Reports
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