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circulating tumour DNA

Hongdo Do, Daniel Cameron, Ramyar Molania, Bibhusal Thapa, Gareth Rivalland, Paul L Mitchell, Carmel Murone, Thomas John, Anthony Papenfuss, Alexander Dobrovic
Identifying circulating tumour DNA (ctDNA) for monitoring of cancer therapy is dependent on the development of readily designed, sensitive cancer-specific DNA markers. Genomic rearrangements that are present in the vast majority of cancers provide such markers.Tumour DNA isolated from two fresh-frozen lung tumours underwent whole genome sequencing. Genomic rearrangements were detected using a new computational algorithm, GRIDSS. Four genomic rearrangements from each tumour were chosen for further study using rearrangement-specific primers...
2016: Advances in Experimental Medicine and Biology
Elena Trujillo-Arribas, Hada C Macher, Pilar Jiménez-Arriscado, Fernando de la Portilla, Patrocinio Molinero, Juan M Guerrero, Amalia Rubio
Genomic characterization of cell-free circulating tumour DNA (ctDNA) may offer an opportunity to assess clonal dynamics throughout the course of a patient's illness. The existence of KRAS driver mutations in colon cancer patients is determinant to decide their treatment and to predict their outcome. DNA is extracted automatically from 400 μL of serum using the MagNa Pure Compact with the Nucleic Acid Isolation Kit I. DNA amplification, COLD-PCR and HRM were performed in the same run in the Light Cycler 480...
2016: Advances in Experimental Medicine and Biology
Carles Escriu, John K Field
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Disease
B O'Leary, N C Turner
No abstract text is available yet for this article.
October 4, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Alex F Herrera, Haesook T Kim, Katherine A Kong, Malek Faham, Heather Sun, Aliyah R Sohani, Edwin P Alyea, Victoria E Carlton, Yi-Bin Chen, Corey S Cutler, Vincent T Ho, John Koreth, Chitra Kotwaliwale, Sarah Nikiforow, Jerome Ritz, Scott J Rodig, Robert J Soiffer, Joseph H Antin, Philippe Armand
Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes...
October 6, 2016: British Journal of Haematology
Henri Schmidt, Arutha Kulasinghe, Liz Kenny, Chamindie Punyadeera
Developing non-invasive diagnostic tools in the field of head and neck oncology has been a challenge. Analysis of circulating tumour derivatives in a patient's blood has been explored in other solid cancers. This includes analysis of circulating tumour DNA, intact circulating tumour cells (CTCs) and exosomes. These circulating tumour derivatives provide avenues of investigation which can be representative of a patient's primary tumour signature and can be assessed from a patient's blood sample. In advanced stage cancer patients, these tumour derivatives are found in higher amounts, attributed to higher cellular turnover (apoptosis, autophagy), lysed CTCs and sloughing from necrotic tumours...
October 2016: Oral Oncology
Pamela J Kaisaki, Anthony Cutts, Niko Popitsch, Carme Camps, Melissa M Pentony, Gareth Wilson, Suzanne Page, Kulvinder Kaur, Dimitris Vavoulis, Shirley Henderson, Avinash Gupta, Mark R Middleton, Ioannis Karydis, Denis C Talbot, Anna Schuh, Jenny C Taylor
Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors...
2016: PloS One
Alexandra R Lewis, Juan W Valle, Mairead G McNamara
Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells (CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms...
August 28, 2016: World Journal of Gastroenterology: WJG
Joonil Jung, Joon Sang Lee, Mark A Dickson, Gary K Schwartz, Axel Le Cesne, Andrea Varga, Rastilav Bahleda, Andrew J Wagner, Edwin Choy, Maja J de Jonge, Madelyn Light, Steve Rowley, Sandrine Macé, James Watters
In tumours that harbour wild-type p53, p53 protein function is frequently disabled by the mouse double minute 2 protein (MDM2, or HDM2 in humans). Multiple HDM2 antagonists are currently in clinical development. Preclinical data indicate that TP53 mutations are a possible mechanism of acquired resistance to HDM2 inhibition; however, this resistance mechanism has not been reported in patients. Utilizing liquid biopsies, here we demonstrate that TP53 mutations appear in circulating cell-free DNA obtained from patients with de-differentiated liposarcoma being treated with an inhibitor of the HDM2-p53 interaction (SAR405838)...
2016: Nature Communications
Nicole Vincent Jordan, Aditya Bardia, Ben S Wittner, Cyril Benes, Matteo Ligorio, Yu Zheng, Min Yu, Tilak K Sundaresan, Joseph A Licausi, Rushil Desai, Ryan M O'Keefe, Richard Y Ebright, Myriam Boukhali, Srinjoy Sil, Maristela L Onozato, Anthony J Iafrate, Ravi Kapur, Dennis Sgroi, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Wilhelm Haas, Shyamala Maheswaran, Daniel A Haber
Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER(+)/HER2(-) primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2...
August 24, 2016: Nature
Can Kockan, Faraz Hach, Iman Sarrafi, Robert H Bell, Brian McConeghy, Kevin Beja, Anne Haegert, Alexander W Wyatt, Stanislav V Volik, Kim N Chi, Colin C Collins, S Cenk Sahinalp
MOTIVATION: Successful development and application of precision oncology approaches require robust elucidation of the genomic landscape of a patient's cancer and, ideally, the ability to monitor therapy-induced genomic changes in the tumour in an inexpensive and minimally invasive manner. Thanks to recent advances in sequencing technologies, "liquid biopsy", the sampling of patient's bodily fluids such as blood and urine, is considered as one of the most promising approaches to achieve this goal...
August 16, 2016: Bioinformatics
G Gremel, R J Lee, M R Girotti, A K Mandal, S Valpione, G Garner, M Ayub, S Wood, D G Rothwell, A Fusi, A Wallace, G Brady, C Dive, N Dhomen, P Lorigan, R Marais
BACKGROUND: The application of precision medicine in oncology requires in-depth characterisation of a patient's tumours and the dynamics of their responses to treatment. PATIENTS AND METHODS: We used next-generation sequencing of circulating cell-free DNA (cfDNA) to monitor the response of a KIT p.L576P-mutant metastatic vaginal mucosal melanoma to sequential targeted, immuno- and chemotherapy. RESULTS: Despite a KIT mutation, the response to imatinib was mixed...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Ian A Cree
The importance of RAS mutation in carcinogenesis is established, and knowledge of an individual cancer's mutation status is important for optimal treatment. Areas covered: This paper is restricted to RAS testing in cancer, and highlights papers relevant to current practice. Expert commentary: Multiple laboratory methods are available for RAS gene analysis. PCR is commonly used to determine RAS status, providing a robust and inexpensive technology for clinical use. Next generation sequencing (NGS) platforms are changing the way in which mutation status is determined, though they require considerable expertise...
October 2016: Expert Review of Molecular Diagnostics
Eugene J H Wee, Yuling Wang, Simon Chang-Hao Tsao, Matt Trau
Sensitive and accurate identification of specific DNA mutations can influence clinical decisions. However accurate diagnosis from limiting samples such as circulating tumour DNA (ctDNA) is challenging. Current approaches based on fluorescence such as quantitative PCR (qPCR) and more recently, droplet digital PCR (ddPCR) have limitations in multiplex detection, sensitivity and the need for expensive specialized equipment. Herein we describe an assay capitalizing on the multiplexing and sensitivity benefits of surface-enhanced Raman spectroscopy (SERS) with the simplicity of standard PCR to address the limitations of current approaches...
2016: Theranostics
Kjetil Søreide, Martin M Watson, Dordi Lea, Oddmund Nordgård, Jon Arne Søreide, Hanne R Hagland
BACKGROUND: More accurate predictive and prognostic biomarkers for patients with colorectal cancer (CRC) primaries or colorectal liver metastasis (CLM) are needed. Outside clinical trials, the translational integration of emerging pathways and novel techniques should facilitate exploration of biomarkers for improved staging and prognosis. METHODS: An observational study exploring predictive and prognostic biomarkers in a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastases...
2016: Journal of Translational Medicine
Jacqueline A Shaw, David S Guttery, Allison Hills, Daniel Fernandez-Garcia, Karen Page, Brenda M Rosales, Kate S Goddard, Robert K Hastings, Jinli Luo, Olivia Ogle, Laura Woodley, Simak Ali, Justin Stebbing, R Charles Coombes
PURPOSE: The purpose of this study was to directly compare mutation profiles in multiple single CTCs and cfDNA isolated from the same blood samples taken from patients with metastaic breast cancer (MBC). We aimed to determine whether cell-free DNA would reflect the heterogeneity observed in 40 single CTCs. EXPERIMENTAL DESIGN: CTCs were enumerated by Cellsearch. CTC count was compared with the quantity of matched cfDNA and serum CA15-3 and alkaline phosphatase (ALP) in 112 patients with metastatic breast cancer...
June 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jacob J Chabon, Andrew D Simmons, Alexander F Lovejoy, Mohammad S Esfahani, Aaron M Newman, Henry J Haringsma, David M Kurtz, Henning Stehr, Florian Scherer, Chris A Karlovich, Thomas C Harding, Kathleen A Durkin, Gregory A Otterson, W Thomas Purcell, D Ross Camidge, Jonathan W Goldman, Lecia V Sequist, Zofia Piotrowska, Heather A Wakelee, Joel W Neal, Ash A Alizadeh, Maximilian Diehn
Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1...
June 10, 2016: Nature Communications
Naoto Hadano, Yoshiaki Murakami, Kenichiro Uemura, Yasusi Hashimoto, Naru Kondo, Naoya Nakagawa, Taijiro Sueda, Eiso Hiyama
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC. METHODS: We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA...
June 28, 2016: British Journal of Cancer
Nicholas Li-Xun Syn, Wei-Peng Yong, Boon-Cher Goh, Soo-Chin Lee
INTRODUCTION: Tumour molecular profiling has been at the crossroads of large-scale integrative genomic studies and major clinical trials over the past 5 years and has provided roadmaps for better disease stratification and therapeutic management. AREAS COVERED: We review the landscape of precision oncology trials in Asia, Europe and the United States, and emerging insights gained from recently reported studies such as the SHIVA and CUSTOM trials. Changes in the molecular portraits of human cancers and the immune contexture of the tumor microenvironment during treatment may predict the course of tumor progression, including the development of treatment resistance...
August 2016: Expert Opinion on Drug Metabolism & Toxicology
Nicola A Pascarelli, Antonella Fioravanti, Elena Moretti, Giacomo M Guidelli, Lucia Mazzi, Giulia Collodel
Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa...
May 17, 2016: Reproduction, Fertility, and Development
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