keyword
https://read.qxmd.com/read/33033274/detection-of-genomic-alterations-in-breast-cancer-with-circulating-tumour-dna-sequencing
#1
Dimitrios Kleftogiannis, Danliang Ho, Jun Xian Liew, Polly S Y Poon, Anna Gan, Raymond Chee-Hui Ng, Benita Kiat-Tee Tan, Kiang Hiong Tay, Swee H Lim, Gek San Tan, Chih Chuan Shih, Tony Kiat-Hon Lim, Ann Siew-Gek Lee, Iain Beehuat Tan, Yoon-Sim Yap, Sarah B Ng
Analysis of circulating cell-free DNA (cfDNA) has opened new opportunities for characterizing tumour mutational landscapes with many applications in genomic-driven oncology. We developed a customized targeted cfDNA sequencing approach for breast cancer (BC) using unique molecular identifiers (UMIs) for error correction. Our assay, spanning a 284.5 kb target region, is combined with a novel freely-licensed bioinformatics pipeline that provides detection of low-frequency variants, and reliable identification of copy number variations (CNVs) directly from plasma DNA...
October 8, 2020: Scientific Reports
https://read.qxmd.com/read/33029662/correlations-between-baseline-18-f-fdg-pet-tumour-parameters-and-circulating-dna-in-diffuse-large-b-cell-lymphoma-and-hodgkin-lymphoma
#2
Pierre Decazes, Vincent Camus, Elodie Bohers, Pierre-Julien Viailly, Hervé Tilly, Philippe Ruminy, Mathieu Viennot, Sébastien Hapdey, Isabelle Gardin, Stéphanie Becker, Pierre Vera, Fabrice Jardin
BACKGROUND: 18 F-FDG PET/CT is a standard for many B cell malignancies, while blood DNA measurements are emerging tools. Our objective was to evaluate the correlations between baseline PET parameters and circulating DNA in diffuse large B cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). METHODS: Twenty-seven DLBCL and forty-eight cHL were prospectively included. Twelve PET parameters were analysed. Spearman's correlations were used to compare PET parameters each other and to circulating cell-free DNA ([cfDNA]) and circulating tumour DNA ([ctDNA])...
October 7, 2020: EJNMMI Research
https://read.qxmd.com/read/33021299/cytotoxic-cis-cis-1-3-5-triaminocyclohexane-ruthenium-ii-diphosphine-complexes-evidence-for-covalent-binding-and-intercalation-with-dna
#3
Dan E Wise, Aimee J Gamble, Sham W Arkawazi, Paul H Walton, M Carmen Galan, Michael P O'Hagan, Karen G Hogg, Joanne L Marrison, Peter J O'Toole, Hazel A Sparkes, Jason M Lynam, Paul G Pringle
We report cytotoxic ruthenium(ii) complexes of the general formula [RuCl(cis-tach)(diphosphine)]+ (cis-tach = cis-cis-1,3,5-triaminocyclohexane) that have been characterised by 1H, 13C and 31P{1H} NMR spectroscopy, mass spectrometry, X-ray crystallography and elemental analysis. The kinetics of aquation and stability of the active species have been studied, showing that the chlorido ligand is substituted by water at 298 K with first order rate constants of 10-2-10-3 s-1, ideal for potential clinical use as anti-tumour agents...
October 6, 2020: Dalton Transactions: An International Journal of Inorganic Chemistry
https://read.qxmd.com/read/32970854/the-detection-of-isochromosome-i-12p-in-malignant-germ-cell-tumours-and-tumours-with-somatic-malignant-transformation-using-qpcr
#4
Alexander Fichtner, Annika Richter, Simon Filmar, Nadine T Gaisa, Stefan Schweyer, Henning Reis, Daniel Nettersheim, Christoph Oing, Fabian A Gayer, Andreas Leha, Stefan Küffer, Philipp Ströbel, Silke Kaulfuß, Felix Bremmer
Malignant germ cell tumours (GCT) of the testis are rare neoplasms, but the most common solid malignancy of young men. WHO guidelines divide GCT into five types for which numerous immunohistochemical markers allow the exact histological subtyping in the majority of the cases. In contrast, the germ cell origin is often hard to prove in metastatic GCT that have developed so-called somatic malignant transformation. A high percentage of up to 89% of germ cell tumours are characterized by the appearance of an isochromosome 12p (i[12p])...
September 24, 2020: Histopathology
https://read.qxmd.com/read/32968207/clinical-relevance-of-blood-based-ctdna-analysis-mutation-detection-and-beyond
#5
REVIEW
Laura Keller, Yassine Belloum, Harriet Wikman, Klaus Pantel
Cell-free DNA (cfDNA) derived from tumours is present in the plasma of cancer patients. The majority of currently available studies on the use of this circulating tumour DNA (ctDNA) deal with the detection of mutations. The analysis of cfDNA is often discussed in the context of the noninvasive detection of mutations that lead to resistance mechanisms and therapeutic and disease monitoring in cancer patients. Indeed, substantial advances have been made in this area, with the development of methods that reach high sensitivity and can interrogate a large number of genes...
September 24, 2020: British Journal of Cancer
https://read.qxmd.com/read/32967919/comparison-of-three-commercial-decision-support-platforms-for-matching-of-next-generation-sequencing-results-with-therapies-in-patients-with-cancer
#6
Samantha O Perakis, Sabrina Weber, Qing Zhou, Ricarda Graf, Sabine Hojas, Jakob M Riedl, Armin Gerger, Nadia Dandachi, Marija Balic, Gerald Hoefler, Ed Schuuring, Harry J M Groen, Jochen B Geigl, Ellen Heitzer, Michael R Speicher
OBJECTIVE: Precision oncology depends on translating molecular data into therapy recommendations. However, with the growing complexity of next-generation sequencing-based tests, clinical interpretation of somatic genomic mutations has evolved into a formidable task. Here, we compared the performance of three commercial clinical decision support tools, that is, NAVIFY Mutation Profiler (NAVIFY; Roche), QIAGEN Clinical Insight (QCI) Interpret (QIAGEN) and CureMatch Bionov (CureMatch). METHODS: In order to obtain the current status of the respective tumour genome, we analysed cell-free DNA from patients with metastatic breast, colorectal or non-small cell lung cancer...
September 2020: ESMO Open
https://read.qxmd.com/read/32953487/egfr-circulating-tumour-dna-testing-identification-of-predictors-of-ctdna-detection-and-implications-for-survival-outcomes
#7
Alexandra Pender, Curtis Hughesman, Elaine Law, Amadea Kristanti, Kelly McNeil, Selina Wong, Tracy Tucker, Ian Bosdet, Sean Young, Janessa Laskin, Aly Karsan, Stephen Yip, Cheryl Ho
Background: EGFR T790M testing is the standard of care for activating EGFR mutation (EGFRm) non-small cell lung cancer (NSCLC) progressing on 1st/2nd generation TKIs to select patients for osimertinib. Despite sensitive assays, detection of circulating tumour deoxyribonucleic acid (ctDNA) is variable and influenced by clinical factors. The number and location of sites of progressive disease at time of testing were reviewed to explore the effect on EGFR ctDNA detection. The prognostic value of EGFR ctDNA detection on survival outcomes was assessed...
August 2020: Translational Lung Cancer Research
https://read.qxmd.com/read/32884537/baseline-plasma-egfr-circulating-tumour-dna-levels-in-a-pilot-cohort-of-egfr-mutant-limited-stage-lung-adenocarcinoma-patients-undergoing-radical-lung-radiotherapy
#8
Brendan Seng Hup Chia, Wen Long Nei, Sabanayagam Charumathi, Kam Weng Fong, Min-Han Tan
The use of circulating cell-free tumour DNA (ctDNA) is established in metastatic lung adenocarcinoma to detect and monitor sensitising EGFR mutations. In early-stage disease, there is very little data supporting its role as a potential biomarker. We report on a prospective cohort of 9 limited-stage EGFR mutant lung cancer patients who were treated with radical radiotherapy. We looked at baseline plasma EGFR ctDNA and noted the detection rates to be higher in locally advanced disease. At a median follow-up of 13...
May 2020: Case Reports in Oncology
https://read.qxmd.com/read/32873154/phenotypes-from-cell-free-dna
#9
Alexis Zukowski, Satyanarayan Rao, Srinivas Ramachandran
Cell-free DNA (cfDNA) has the potential to enable non-invasive detection of disease states and progression. Beyond its sequence, cfDNA also represents the nucleosomal landscape of cell(s)-of-origin and captures the dynamics of the epigenome. In this review, we highlight the emergence of cfDNA epigenomic methods that assess disease beyond the scope of mutant tumour genotyping. Detection of tumour mutations is the gold standard for sequencing methods in clinical oncology. However, limitations inherent to mutation targeting in cfDNA, and the possibilities of uncovering molecular mechanisms underlying disease, have made epigenomics of cfDNA an exciting alternative...
September 2020: Open Biology
https://read.qxmd.com/read/32830120/positive-tumour-cd47-expression-is-an-independent-prognostic-factor-for-recurrence-in-resected-non-small-cell-lung-cancer
#10
Yan Xu, Ji Li, Bing Tong, Minjiang Chen, Xiaoyan Liu, Wei Zhong, Jing Zhao, Mengzhao Wang
BACKGROUND: Immunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy. PATIENTS AND METHODS: CD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group...
August 2020: ESMO Open
https://read.qxmd.com/read/32807235/detection-of-ctdna-in-plasma-of-patients-with-clinically-localised-prostate-cancer-is-associated-with-rapid-disease-progression
#11
Edmund Lau, Patrick McCoy, Fairleigh Reeves, Ken Chow, Michael Clarkson, Edmond M Kwan, Kate Packwood, Helen Northen, Miao He, Zoya Kingsbury, Stefano Mangiola, Michael Kerger, Marc A Furrer, Helen Crowe, Anthony J Costello, David J McBride, Mark T Ross, Bernard Pope, Christopher M Hovens, Niall M Corcoran
BACKGROUND: DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown. METHODS: We performed whole-genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations...
August 17, 2020: Genome Medicine
https://read.qxmd.com/read/32774122/potential-of-modern-circulating-cell-free-dna-diagnostic-tools-for-detection-of-specific-tumour-cells-in-clinical-practice
#12
REVIEW
Jernej Gašperšič, Alja Videtič Paska
Personalized medicine is a developing field of medicine that has gained in importance in recent decades. New diagnostic tests based on the analysis of circulating cell-free DNA (cfDNA) were developed as a tool of diagnosing different cancer types. By detecting the subpopulation of mutated DNA from cancer cells, it is possible to detect the presence of a specific tumour in early stages of the disease. Mutation analysis is performed by quantitative polymerase chain reaction (qPCR) or the next generation sequencing (NGS), however, cfDNA protocols need to be modified carefully in preanalytical, analytical, and postanalytical stages...
October 15, 2020: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://read.qxmd.com/read/32752173/cpg-islands-as-markers-for-liquid-biopsies-of-cancer-patients
#13
Maximilian Sprang, Claudia Paret, Joerg Faber
The analysis of tumours using biomarkers in blood is transforming cancer diagnosis and therapy. Cancers are characterised by evolving genetic alterations, making it difficult to develop reliable and broadly applicable DNA-based biomarkers for liquid biopsy. In contrast to the variability in gene mutations, the methylation pattern remains generally constant during carcinogenesis. Thus, methylation more than mutation analysis may be exploited to recognise tumour features in the blood of patients. In this work, we investigated the possibility of using global CpG (CpG means a CG motif in the context of methylation...
August 1, 2020: Cells
https://read.qxmd.com/read/32739405/prognostic-impact-of-total-plasma-cell-free-dna-concentration-in-androgen-receptor-pathway-inhibitor-treated-metastatic-castration-resistant-prostate-cancer
#14
Heidi Fettke, Edmond M Kwan, Patricia Bukczynska, Nicole Ng, Tu Nguyen-Dumont, Melissa C Southey, Ian D Davis, Andrew Mant, Phillip Parente, Carmel Pezaro, Christine Hauser, Arun A Azad
Total plasma cell-free DNA (cfDNA) levels were recently shown to be prognostic in two large phase III trials of taxane chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). However, whether cfDNA concentration is predictive of treatment outcomes with androgen receptor pathway inhibitors (ARPIs) is unknown. We quantified plasma cfDNA levels at baseline (n = 74) and 4 weeks on treatment (n = 56) in a prospective cohort of mCRPC patients treated with the ARPIs abiraterone acetate or enzalutamide...
July 29, 2020: European Urology Focus
https://read.qxmd.com/read/32724107/evaluating-the-quantity-quality-and-size-distribution-of-cell-free-dna-by-multiplex-droplet-digital-pcr
#15
Miguel Alcaide, Matthew Cheung, Jack Hillman, S Rod Rassekh, Rebecca J Deyell, Gerald Batist, Aly Karsan, Alexander W Wyatt, Nathalie Johnson, David W Scott, Ryan D Morin
Cell-free DNA (cfDNA) has become a comprehensive biomarker in the fields of non-invasive cancer detection and monitoring, organ transplantation, prenatal genetic testing and pathogen detection. While cfDNA samples can be obtained using a broad variety of approaches, there is an urgent need to standardize analytical tools aimed at assessing its basic properties. Typical methods to determine the yield and fragment size distribution of cfDNA samples are usually either blind to genomic DNA contamination or the presence of enzymatic inhibitors, which can confound and undermine downstream analyses...
July 28, 2020: Scientific Reports
https://read.qxmd.com/read/32707646/cux1-transcriptional-master-regulator-of-tumor-progression-in-pancreatic-neuroendocrine-tumors
#16
Sebastian Krug, Julia Weissbach, Annika Blank, Aurel Perren, Johannes Haybaeck, Volker Fendrich, Anja Rinke, Thomas Mathias Gress, Jonas Rosendahl, Patrick Michl
Recently, we identified the homeodomain transcription factor Cut homeobox 1 (CUX1) as mediator of tumour de-differentiation and metastatic behaviour in human insulinoma patients. In insulinomas, CUX1 enhanced tumour progression by stimulating proliferation and angiogenesis in vitro and in vivo. In patients with non-functional pancreatic neuroendocrine tumours (PanNET), however, the impact of CUX1 remains to be elucidated. Here, we analysed CUX1 expression in two large independent cohorts ( n = 43 and n = 141 tissues) of non-functional treatment-naïve and pre-treated PanNET patients, as well as in the RIP1Tag2 mouse model of pancreatic neuroendocrine tumours...
July 19, 2020: Cancers
https://read.qxmd.com/read/32687856/dynamics-of-cell-free-tumour-dna-correlate-with-treatment-response-of-head-and-neck-cancer-patients-receiving-radiochemotherapy
#17
Franz J Hilke, Francesc Muyas, Jakob Admard, Beate Kootz, Dominik Nann, Stefan Welz, Olaf Rieß, Daniel Zips, Stephan Ossowski, Christopher Schroeder, Kerstin Clasen
PURPOSE: Definitive radiochemotherapy (RCTX) with curative intent is one of the standard treatment options in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Despite this intensive therapy protocol, disease recurrence remains an issue. Therefore, we tested the predictive capacity of liquid biopsies as a novel biomarker during RCTX in patients with HNSCC. MATERIAL AND METHODS: We sequenced the tumour samples of 20 patients with locally advanced HNSCC to identify driver mutations...
July 17, 2020: Radiotherapy and Oncology
https://read.qxmd.com/read/32662719/minimally-invasive-classification-of-paediatric-solid-tumours-using-reduced-representation-bisulphite-sequencing-of-cell-free-dna-a-proof-of-principle-study
#18
Ruben Van Paemel, Andries De Koker, Charlotte Vandeputte, Lieke van Zogchel, Tim Lammens, Geneviève Laureys, Jo Vandesompele, Gudrun Schleiermacher, Mathieu Chicard, Nadine Van Roy, Ales Vicha, G A M Tytgat, Nico Callewaert, Katleen De Preter, Bram De Wilde
In the clinical management of paediatric solid tumours, histological examination of tumour tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumour is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumour samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of paediatric tumours using cell-free reduced representation bisulphite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples...
July 14, 2020: Epigenetics: Official Journal of the DNA Methylation Society
https://read.qxmd.com/read/32660824/dna-damage-measured-in-blood-cells-predicts-overall-and-progression-free-survival-in-germ-cell-tumour-patients
#19
Zuzana Sestakova, Katarina Kalavska, Bozena Smolkova, Vera Miskovska, Katarina Rejlekova, Zuzana Sycova-Mila, Patrik Palacka, Jana Obertova, Andrea Holickova, Lenka Hurbanova, Dana Jurkovicova, Jan Roska, Eduard Goffa, Daniela Svetlovska, Michal Chovanec, Jozef Mardiak, Michal Mego, Miroslav Chovanec
Germ cell tumour (GCT) patients who fail to respond to chemotherapy or who relapse have a poor prognosis. Timely and accurately stratifying such patients could optimise their therapy. We identified endogenous DNA damage levels as a prognostic marker for progression-free (PFS) and overall (OS) survival in chemotherapy-naïve GCT patients. In the present study, we have extended our previous results and reviewed the prognostic power of DNA damage level in GCTs. Endogenous DNA damage levels were measured with the comet assay...
June 2020: Mutation Research
https://read.qxmd.com/read/32630266/circulating-cell-free-dna-based-liquid-biopsy-markers-for-the-non-invasive-prognosis-and-monitoring-of-metastatic-pancreatic-cancer
#20
Marta Toledano-Fonseca, M Teresa Cano, Elizabeth Inga, Rosa Rodríguez-Alonso, M Auxiliadora Gómez-España, Silvia Guil-Luna, Rafael Mena-Osuna, Juan R de la Haba-Rodríguez, Antonio Rodríguez-Ariza, Enrique Aranda
Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue...
July 1, 2020: Cancers
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