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
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
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
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
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
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
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
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
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
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
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
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
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
Jingde Chen, Ming Quan, Zhiqin Chen, Tianmei Zeng, Yandong Li, Ying Zhou, Yanan Hai, Yong Gao
PURPOSE: Patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) cancers are prone to response to programmed cell death-1 (PD-1) checkpoint inhibitors. Therefore, we explored the efficacy and safety of a PD-1 checkpoint inhibitor camrelizumab in advanced or metastatic solid tumour with dMMR/MSI-H. METHODS: Patients with dMMR/MSI-H advanced or metastatic solid tumours who had received at least one line of prior systemic chemotherapy were recruited...
July 4, 2020: Journal of Cancer Research and Clinical Oncology
Nicholas Eastley, Aurore Sommer, Barbara Ottolini, Rita Neumann, Jin-Li Luo, Robert K Hastings, Thomas McCulloch, Claire P Esler, Jacqueline A Shaw, Robert U Ashford, Nicola J Royle
Soft tissue sarcomas (STS) are rare, malignant tumours with a generally poor prognosis. Our aim was to explore the potential of cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) analysis to track non-metastatic STS patients undergoing attempted curative treatment. The analysed cohort ( n = 29) contained multiple STS subtypes including myxofibrosarcomas, undifferentiated pleomorphic sarcomas, leiomyosarcomas, and dedifferentiated liposarcomas amongst others. Perioperative cfDNA levels trended towards being elevated in patients ( p = 0...
June 24, 2020: International Journal of Molecular Sciences
Arian Lundberg, Linda S Lindström, Joel S Parker, Elinor Löverli, Charles M Perou, Jonas Bergh, Nicholas P Tobin
Pan-cancer genomic analyses based on the magnitude of pathway activity are currently lacking. Focusing on the cell cycle, we examined the DNA mutations and chromosome arm-level aneuploidy within tumours with low, intermediate and high cell-cycle activity in 9515 pan-cancer patients with 32 different tumour types. Boxplots showed that cell-cycle activity varied broadly across and within all cancers. TP53 and PIK3CA mutations were common in all cell cycle score (CCS) tertiles but with increasing frequency as cell-cycle activity levels increased (P < 0...
June 24, 2020: Oncogene
Satoshi Murahashi, Takashi Akiyoshi, Takeshi Sano, Yosuke Fukunaga, Tetsuo Noda, Masashi Ueno, Hitoshi Zembutsu
BACKGROUND: The "watch-and-wait" approach is a common treatment option amongst patients with locally advanced rectal cancer (LARC). However, the diagnostic sensitivity of clinical modalities, such as colonoscopy and magnetic resonance imaging to determine pathological response, is not high. We analysed the clinical utility of circulating tumour DNA (ctDNA) of patients with LARC to predict response to preoperative therapy and postoperative recurrence. METHODS: A serial ctDNA analysis of 222 plasma samples from 85 patients with LARC was performed using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with over 240 hotspots...
June 22, 2020: British Journal of Cancer
Johann S de Bono, Christina Guo, Bora Gurel, Angelo M De Marzo, Karen S Sfanos, Ram S Mani, Jesús Gil, Charles G Drake, Andrea Alimonti
Prostate cancer is a major cause of cancer morbidity and mortality. Intra-prostatic inflammation is a risk factor for prostate carcinogenesis, with diet, chemical injury and an altered microbiome being causally implicated. Intra-prostatic inflammatory cell recruitment and expansion can ultimately promote DNA double-strand breaks and androgen receptor activation in prostate epithelial cells. The activation of the senescence-associated secretory phenotype fuels further 'inflammatory storms', with free radicals leading to further DNA damage...
August 2020: Nature Reviews. Cancer
Thomas Weiland, Alexander Eckert, Peter Valentin Tomazic, Axel Wolf, Prisca Pondorfer, Sarah Vasicek, Matthias Graupp, Clemens Holzmeister, Ulrich Moser, Alexandros Andrianakis, Georg Kangler, Peter Kiss, Luka Brcic, Matthias Kappler, Claudia Wickenhauser, Anja Haak, Maximilian Krüger, Bilal Al-Nawas, Sebastian Blatt, Norbert Brockmeyer, Adriane Skaletz-Rorowski, Anja Potthoff, Lars E French, Sara Charnowski, Markus Reinholz, Andreas M Kaufmann, Sarah Thies, Hans-Georg Lambrecht, Barbara Seliger, Dominik C Wild, Dietmar Thurnher
BACKGROUND: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay. METHODS: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies...
June 11, 2020: EBioMedicine
Abu Ali Ibn Sina, Ting-Yun Lin, Ramanathan Vaidyanathan, Zhaoran Wang, Shuvashis Dey, Jing Wang, Andreas Behren, Alain Wuethrich, Laura G Carrascosa, Matt Trau
Extracellular vesicles (EV) play a major role in intercellular communication by transmitting cellular materials (e.g. protein, RNA) among distant cells. Recent evidence suggests that they could also contribute to carrying DNA which could inform on the mutational status of the parent tumour DNA. Thus, the fundamental analysis of evDNA could open a better understanding of tumour metastasis and provide new pathways for noninvasive detection and monitoring of cancer. To explore the potential of evDNA for diagnostics, the isolation of pure evDNA from body fluids free of cfDNA contamination is crucial...
June 12, 2020: Nanoscale Horizons: the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy
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