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https://www.readbyqxmd.com/read/28306358/the-genetics-of-gastroesophageal-adenocarcinoma-and-the-use-of-circulating-cell-free-dna-for-disease-detection-and-monitoring
#1
Mark R Openshaw, Catherine J Richards, David S Guttery, Jacqueline A Shaw, Anne L Thomas
Gastroesophageal adenocarcinoma (GOA) is a frequently occurring cancer worldwide with a poor clinical outcome. Adenocarcinomas of the oesophagus and gastroesophageal junction have shown a recent increase in frequency, therefore there is need to increase our understanding of GOA in order to improve our ability to detect, monitor and treat the disease. Areas covered: The authors discuss the current classification of GOA in the context of recent changes in incidence. The authors also discuss developments in the understanding of disease biology and recent discoveries from whole genome and whole exome sequencing, and studies in immunotherapy...
March 17, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#2
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28252003/integrating-liquid-biopsies-into-the-management-of-cancer
#3
REVIEW
Giulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli
During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly...
March 2, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28222152/alteration-of-the-exdna-profile-in-blood-serum-of-llc-bearing-mice-under-the-decrease-of-tumour-invasion-potential-by-bovine-pancreatic-dnase-i-treatment
#4
Ludmila A Alekseeva, Nadezhda L Mironova, Evgenyi V Brenner, Alexander M Kurilshikov, Olga A Patutina, Marina A Zenkova
Taking into account recently obtained data indicating the participation of circulating extracellular DNA (exDNA) in tumorigenesis, enzymes with deoxyribonucleic activity have again been considered as potential antitumour and antimetastatic drugs. Previously, using murine Lewis lung carcinoma and hepatocellular carcinoma A1 tumour models, we have shown the antimetastatic activity of bovine DNase I, which correlates with an increase of DNase activity and a decrease of exDNA concentration in the blood serum of tumour-bearing mice...
2017: PloS One
https://www.readbyqxmd.com/read/28211676/electrochemical-genetic-profiling-of-single-cancer-cells
#5
Josep Ll Acero Sánchez, Hamdi Joda, Olivier Y F Henry, Beata W Solnestam, Linda Kvastad, Pelin S Akan, Joakim Lundeberg, Nadja Laddach, Dheeraj Ramakrishnan, Ian Riley, Carmen Schwind, Daniel Latta, Ciara K O'Sullivan
Recent understandings in the development and spread of cancer have led to the realization of novel single cell analysis platforms focused on circulating tumor cells (CTCs). A simple, rapid, and inexpensive analytical platform capable of providing genetic information on these rare cells is highly desirable to support clinicians and researchers alike to either support the selection or adjustment of therapy or provide fundamental insights into cell function and cancer progression mechanisms. We report on the genetic profiling of single cancer cells, exploiting a combination of multiplex ligation-dependent probe amplification (MLPA) and electrochemical detection...
March 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28194229/circulating-and-tissue-biomarkers-in-early-stage-non-small-cell-lung-cancer
#6
Caterina Fumagalli, Fabrizio Bianchi, Paola Rafaniello Raviele, Davide Vacirca, Giovanni Bertalot, Cristiano Rampinelli, Matteo Lazzeroni, Bernardo Bonanni, Giulia Veronesi, Nicola Fusco, Massimo Barberis, Elena Guerini-Rocco
OBJECTIVE: We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). MATERIALS AND METHODS: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test)...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28126926/molecular-disease-monitoring-using-circulating-tumor-dna-in-myelodysplastic-syndromes
#7
Paul Yeh, Michael Dickinson, Sarah Ftouni, Tane Hunter, Devbarna Sinha, Stephen Q Wong, Rishu Agarwal, Ravikiran Vedururu, Kenneth Doig, Chun Yew Fong, Piers Blombery, David Westerman, Mark A Dawson, Sarah-Jane Dawson
The diagnosis and monitoring of myelodysplastic syndromes (MDS) are highly reliant on bone marrow morphology, which is associated with substantial inter-observer variability. Azacitidine is the mainstay of treatment in MDS, however only half of all patients respond. Therefore, there is an urgent need for improved modalities for the diagnosis and monitoring of MDS. The majority of MDS patients have either clonal somatic karyotypic abnormalities and/or gene mutations that aid in the diagnosis and can be used to monitor treatment response...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/28104619/osimertinib-benefit-in-egfr-mutant-nsclc-patients-with-t790m-mutation-detected-by-circulating-tumour-dna
#8
J Remon, C Caramella, C Jovelet, L Lacroix, A Lawson, S Smalley, K Howarth, D Gale, E Green, V Plagnol, N Rosenfeld, D Planchard, M V Bluthgen, A Gazzah, C Pannet, C Nicotra, E Auclin, J C Soria, B Besse
BACKGROUND: Approximately 50% of Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. MATERIAL AND METHODS: ctDNA T790M mutational status was assessed by Inivata InVision(TM) (eTAm-Seq(TM)) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016...
January 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28104311/comprehensive-profiling-of-the-androgen-receptor-in-liquid-biopsies-from-castration-resistant-prostate-cancer-reveals-novel-intra-ar-structural-variation-and-splice-variant-expression-patterns
#9
Bram De Laere, Pieter-Jan van Dam, Tom Whitington, Markus Mayrhofer, Emanuela Henao Diaz, Gert Van den Eynden, Jean Vandebroek, Jurgen Del-Favero, Steven Van Laere, Luc Dirix, Henrik Grönberg, Johan Lindberg
BACKGROUND: Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. OBJECTIVE: To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. DESIGN, SETTING, AND PARTICIPANTS: Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy...
January 16, 2017: European Urology
https://www.readbyqxmd.com/read/28102343/individualised-multiplexed-circulating-tumour-dna-assays-for-monitoring-of-tumour-presence-in-patients-after-colorectal-cancer-surgery
#10
Sarah B Ng, Clarinda Chua, Matthew Ng, Anna Gan, Polly Sy Poon, Melissa Teo, Cherylin Fu, Wei Qiang Leow, Kiat Hon Lim, Alexander Chung, Si-Lin Koo, Su Pin Choo, Danliang Ho, Steve Rozen, Patrick Tan, Mark Wong, William F Burkholder, Iain Beehuat Tan
Circulating tumour DNA (ctDNA) has the potential to be a specific biomarker for the monitoring of tumours in patients with colorectal cancer (CRC). Here, our aim was to develop a personalised surveillance strategy to monitor the clinical course of CRC after surgery. We developed patient-specific ctDNA assays based on multiplexed detection of somatic mutations identified from patient primary tumours, and applied them to detect ctDNA in 44 CRC patients, analysing a total of 260 plasma samples. We found that ctDNA detection correlated with clinical events - it is detectable in pre-operative but not post-operative plasma, and also in patients with recurrent CRC...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096542/liquid-biopsy-in-2016-circulating-tumour-cells-and-cell-free-dna-in-gastrointestinal-cancer
#11
Klaus Pantel, Catherine Alix-Panabières
No abstract text is available yet for this article.
February 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28075351/circulating-nucleosomes-and-nucleosome-modifications-as-biomarkers-in-cancer
#12
REVIEW
Peter McAnena, James A L Brown, Michael J Kerin
Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment...
January 8, 2017: Cancers
https://www.readbyqxmd.com/read/28061772/use-of-liquid-biopsies-to-monitor-disease-progression-in-a-sarcoma-patient-a-case-report
#13
Heidi M Namløs, Olga Zaikova, Bodil Bjerkehagen, Daniel Vodák, Eivind Hovig, Ola Myklebost, Kjetil Boye, Leonardo A Meza-Zepeda
BACKGROUND: Many patients experience local recurrence or metastases after receiving potentially curative treatment, and early detection of these events is important for disease control. Recent technological advances make it possible to use blood plasma containing circulating cell-free tumour DNA (ctDNA) as a liquid biopsy. In this case report we show how serial liquid biopsies can be used to monitor the disease course and detect disease recurrence in a sarcoma patient. CASE PRESENTATION: A 55-year-old male presented with a rapidly growing, painful palpable mass in the left groin region, and a biopsy revealed a high-grade malignant spindle cell sarcoma...
January 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28060738/the-prognostic-value-of-clonal-heterogeneity-and-quantitative-assessment-of-plasma-circulating-clonal-ig-vdj-sequences-at-diagnosis-in-patients-with-follicular-lymphoma
#14
Clémentine Sarkozy, Sarah Huet, Victoria E H Carlton, Bettina Fabiani, Alain Delmer, Fabrice Jardin, Marie-Helene Delfau-Larue, Maya Hacini, Vincent Ribrag, Stéphanie Guidez, Malek Faham, Gilles Salles
Recent advances in next-generation sequencing (NGS) have enabled the quantitation of circulating tumour DNA (ctDNA) encoding the clonal rearranged V(D)J immunoglobulin locus. We aimed to evaluate the clonal heterogeneity of follicular lymphoma (FL) in the tumour and the plasma at diagnosis and to assess the prognostic value of the ctDNA level. Plasma samples at diagnosis were available for 34 patients registered in the PRIMA trial (NCT00140582). One tumour clonotype or more could be detected for 29 (85%) and 25 (74%) patients, respectively, in the tumour or plasma samples...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28007619/malignant-mesothelioma-biomarkers-from-discovery-to-use-in-clinical-practise-for-diagnosis-monitoring-screening-and-treatment
#15
REVIEW
Jenette Creaney, Bruce W S Robinson
Malignant pleural mesothelioma is a highly aggressive tumour associated with asbestos exposure. There are few effective treatment options for mesothelioma and patients have a very poor prognosis with a median survival of less than 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management and the search for a mesothelioma biomarker has been on-going for the past thirty years. Many traditional soluble (glyco)-protein biomarkers have been evaluated over this time and an ever increasing list of new biomarkers, including mRNA, DNA, miRNA and antibodies, are being reported from biomarker discovery projects...
December 19, 2016: Chest
https://www.readbyqxmd.com/read/28006816/egfr-mutation-detection-in-circulating-cell-free-dna-of-lung-adenocarcinoma-patients-analysis-of-lux-lung-3-and-6
#16
Yi-Long Wu, Lecia V Sequist, Cheng-Ping Hu, Jifeng Feng, Shun Lu, Yunchao Huang, Wei Li, Mei Hou, Martin Schuler, Tony Mok, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Neil Gibson, Dan Massey, Miyoung Kim, James Chih-Hsin Yang
BACKGROUND: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). METHODS: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit...
January 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27999407/tumour-heterogeneity-the-key-advantages-of-single-cell-analysis
#17
REVIEW
Marta Tellez-Gabriel, Benjamin Ory, Francois Lamoureux, Marie-Francoise Heymann, Dominique Heymann
Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies...
December 20, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27997533/exploratory-analysis-of-tp53-mutations-in-circulating-tumour-dna-as-biomarkers-of-treatment-response-for-patients-with-relapsed-high-grade-serous-ovarian-carcinoma-a-retrospective-study
#18
Christine A Parkinson, Davina Gale, Anna M Piskorz, Heather Biggs, Charlotte Hodgkin, Helen Addley, Sue Freeman, Penelope Moyle, Evis Sala, Karen Sayal, Karen Hosking, Ioannis Gounaris, Mercedes Jimenez-Linan, Helena M Earl, Wendi Qian, Nitzan Rosenfeld, James D Brenton
BACKGROUND: Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). METHODS AND FINDINGS: We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27994225/comparison-of-circulating-tumour-cells-and-circulating-cell-free-epstein-barr-virus-dna-in-patients-with-nasopharyngeal-carcinoma-undergoing-radiotherapy
#19
Jess Honganh Vo, Wen Long Nei, Min Hu, Wai Min Phyo, Fuqiang Wang, Kam Weng Fong, Terence Tan, Yoke Lim Soong, Shie Lee Cheah, Kiattisa Sommat, Huiyu Low, Belinda Ling, Johnson Ng, Wan Loo Tan, Kian Sing Chan, Lynette Oon, Jackie Y Ying, Min-Han Tan
Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used in clinical settings as a circulating biomarker in nasopharyngeal carcinoma (NPC), but there has been no comparison with circulating tumour cells (CTCs). Our study aims to compare the performance of CTC enumeration against EBV cfDNA quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples from 46 NPC patients at baseline and one month after radiotherapy with or without concurrent chemotherapy were analysed...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27983717/evaluation-of-methylation-biomarkers-for-detection-of-circulating-tumor-dna-and-application-to-colorectal-cancer
#20
Susan M Mitchell, Thu Ho, Glenn S Brown, Rohan T Baker, Melissa L Thomas, Aidan McEvoy, Zheng-Zhou Xu, Jason P Ross, Trevor J Lockett, Graeme P Young, Lawrence C LaPointe, Susanne K Pedersen, Peter L Molloy
Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA...
December 15, 2016: Genes
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