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
Cameron Herberts, Andrew J Murtha, Simon Fu, Gang Wang, Elena Schönlau, Hui Xue, Dong Lin, Anna Gleave, Steven Yip, Arkhjamil Angeles, Sebastien Hotte, Ben Tran, Scott North, Sinja Taavitsainen, Kevin Beja, Gillian Vandekerkhove, Elie Ritch, Evan Warner, Fred Saad, Nayyer Iqbal, Matti Nykter, Martin E Gleave, Yuzhuo Wang, Matti Annala, Kim N Chi, Alexander W Wyatt
BACKGROUND: Activating mutations in AKT1 and PIK3CA are undercharacterised in metastatic castration-resistant prostate cancer (mCRPC), but are linked to activation of phosphatidylinositol 3-kinase (PI3K) signalling and sensitivity to pathway inhibitors in other cancers. OBJECTIVE: To determine the prevalence, genomic context, and clinical associations of AKT1/PIK3CA activating mutations in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: We analysed targeted cell-free DNA (cfDNA) sequencing data from 599 metastatic prostate cancer patients with circulating tumour DNA (ctDNA) content above 2%...
May 22, 2020: European Urology
D C L Vessies, M J E Greuter, K L van Rooijen, T C Linders, M Lanfermeijer, K L Ramkisoensing, G A Meijer, M Koopman, V M H Coupé, G R Vink, R J A Fijneman, D van den Broek
Multiple platforms are commercially available for the detection of circulating cell-free tumour DNA (ctDNA) from liquid biopsies. Since platforms have different input and output variables, deciding what platform to use for a given clinical or research question can be daunting. This study aimed to provide insight in platform selection criteria by comparing four commercial platforms that detect KRAS ctDNA hotspot mutations: Bio-Rad droplet digital PCR (ddPCR), BioCartis Idylla, Roche COBAS z480 and Sysmex BEAMing...
May 15, 2020: Scientific Reports
Maja Svetličič, Anton Bomhard, Christoph Sterr, Fabian Brückner, Magdalena Płódowska, Halina Lisowska, Lovisa Lundholm
Compact chromatin is linked to a poor tumour prognosis and resistance to radiotherapy from photons. We investigated DNA damage induction and repair in the context of chromatin structure for densely ionising alpha radiation as well as its therapeutic potential. Chromatin opening by histone deacetylase inhibitor trichostatin A (TSA) pretreatment reduced clonogenic survival and increased γH2AX foci in MDA-MB-231 cells, indicative of increased damage induction by free radicals using gamma radiation. In contrast, TSA pretreatment tended to improve survival after alpha radiation while γH2AX foci were similar or lower; therefore, an increased DNA repair is suggested due to increased access of repair proteins...
May 8, 2020: Cells
M R Alves-Motta, V Luz-Carvalho, D C S Nunes-Pinheiro, K R Groch, L Gonçalves-Pereira, A M Sánchez-Sarmiento, C Sacristán, J L Catão-Dias, J Díaz-Delgado
We report the pathological features of a facial squamous cell carcinoma (SCC) and an abdominal peripheral nerve sheath tumour (PNST) with rhabdomyoblastic differentiation in an aged free-ranging rough-toothed dolphin (Steno bredanensis). The animal was found stranded dead in poor body condition. On external examination, there was a 25 × 7 × 3 cm extensively ulcerated area on the right maxillary region of the rostrum, involving the oral mucocutaneous junction with prominent nodular edges, severe soft tissue loss and extensive maxillary and premaxillary bone lysis...
April 2020: Journal of Comparative Pathology
Mairéad G McNamara, Jean-Yves Scoazec, Thomas Walter
Patients with extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PD-NECs) have a poor prognosis. Surgery is offered for those with localised disease, but the majority of patients present with advanced disease. Treatment strategies adopted are analogous to that of high grade NECs of the lung, with platinum/etoposide-based regimens advocated in the first-line setting for advanced disease. There is no standard second-line therapy. Research into their molecular and immune pathways may pave the way for novel drug discovery...
July 2020: Endocrine-related Cancer
Kay Brinkman, Lisa Meyer, Anne Bickel, Daniel Enderle, Carola Berking, Johan Skog, Mikkel Noerholm
In addition to Circulating Tumour Cells (CTCs), cell-free DNA (cfDNA) and Extracellular Vesicles (EVs), the notion of "Tumour-Educated Platelets" (TEP) has recently emerged as a potential source of tumour-derived biomarkers accessible through blood liquid biopsies. Here we sought to confirm the suitability of the platelet blood fraction for biomarker detection in comparison to their corresponding EV fraction. As publications have claimed that tumour RNA and other tumour-derived material are transferred from tumour cells to the platelets and that tumour-derived transcripts can be detected in platelets, we chose to focus on RNA carrying a mutation as being of bona fide tumour origin...
2020: Journal of Extracellular Vesicles
Nan Wu, Zhen Zhang, Xi Zhou, Hengqiang Zhao, Yue Ming, Xue Wu, Xian Zhang, Xin-Zhuang Yang, Meng Zhou, Hua Bao, Weisheng Chen, Yong Wu, Sen Liu, Huizi Wang, Yuchen Niu, Yalun Li, Yu Zheng, Yang Shao, Na Gao, Ying Yang, Ying Liu, Wenli Li, Jia Liu, Na Zhang, Xu Yang, Yuan Xu, Mei Li, Yingli Sun, Jianzhong Su, Jianguo Zhang, Weibo Xia, Guixing Qiu, Yong Liu, Jiaqi Liu, Zhihong Wu
Tumour-induced osteomalacia (TIO) is a very rare paraneoplastic syndrome with bone pain, fractures and muscle weakness, which is mostly caused by phosphaturic mesenchymal tumours (PMTs). Cell-free DNA (cfDNA) has been regarded as a non-invasive liquid biopsy for many malignant tumours. However, it has not been studied in benign tumours, which prompted us to adopt the targeted next-generation sequencing approach to compare cfDNAs of 4 TIO patients, four patients with bone metastasis (BM) and 10 healthy controls...
April 11, 2020: Journal of Cellular and Molecular Medicine
Jacob J Chabon, Emily G Hamilton, David M Kurtz, Mohammad S Esfahani, Everett J Moding, Henning Stehr, Joseph Schroers-Martin, Barzin Y Nabet, Binbin Chen, Aadel A Chaudhuri, Chih Long Liu, Angela B Hui, Michael C Jin, Tej D Azad, Diego Almanza, Young-Jun Jeon, Monica C Nesselbush, Lyron Co Ting Keh, Rene F Bonilla, Christopher H Yoo, Ryan B Ko, Emily L Chen, David J Merriott, Pierre P Massion, Aaron S Mansfield, Jin Jen, Hong Z Ren, Steven H Lin, Christina L Costantino, Risa Burr, Robert Tibshirani, Sanjiv S Gambhir, Gerald J Berry, Kristin C Jensen, Robert B West, Joel W Neal, Heather A Wakelee, Billy W Loo, Christian A Kunder, Ann N Leung, Natalie S Lui, Mark F Berry, Joseph B Shrager, Viswam S Nair, Daniel A Haber, Lecia V Sequist, Ash A Alizadeh, Maximilian Diehn
Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2 ; however, a small minority of eligible individuals undergo such screening in the United States3,4 . The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5 , a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic...
April 2020: Nature
Maria Zvereva, Gabriel Roberti, Geoffroy Durand, Catherine Voegele, Minh Dao Nguyen, Tiffany M Delhomme, Priscilia Chopard, Eleonora Fabianova, Zora Adamcakova, Ivana Holcatova, Lenka Foretova, Vladimir Janout, Paul Brennan, Matthieu Foll, Graham B Byrnes, James D McKay, Ghislaine Scelo, Florence Le Calvez-Kelm
BACKGROUND: The DNA released into the bloodstream by malignant tumours· called circulating tumour DNA (ctDNA), is often a small fraction of total cell-free DNA shed predominantly by hematopoietic cells and is therefore challenging to detect. Understanding the biological properties of ctDNA is key to the investigation of its clinical relevance as a non-invasive marker for cancer detection and monitoring. METHODS: We selected 40 plasma DNA samples of pancreatic cancer cases previously reported to carry a KRAS mutation at the 'hotspot' codon 12 and re-screened the cell-free DNA using a 4-size amplicons strategy (57 bp, 79 bp, 167 bp and 218 bp) combined with ultra-deep sequencing in order to investigate whether amplicon lengths could impact on the capacity of detection of ctDNA, which in turn could provide inference of ctDNA and non-malignant cell-free DNA size distribution...
April 2, 2020: EBioMedicine
Kiyoshi Misawa, Yuki Misawa, Masato Mima, Satoshi Yamada, Atsushi Imai, Daiki Mochizuki, Takuya Nakagawa, Tomoya Kurokawa, Shiori Endo, Hideya Kawasaki, John Chadwick Brenner, Hiroyuki Mineta
BACKGROUND: Sal-like protein 4 (SALL4), an embryonic stem cell factor, has been reported to play an essential role in embryogenesis and oncogenesis. As yet, however, the expression and role of this transcription factor in head and neck squamous cell carcinoma (HNSCC) has not been established. METHODS: We assessed SALL4 mRNA expression in a well-characterised dataset of 230 HNSCC samples (test cohort 110 cases and validation cohort 120 cases). We also transfected HNSCC cells (FaDu and UM-SCC-6) with SALL4 siRNA and assessed its effects on proliferation and expression of specific epigenetic factors in order to uncover the role of SALL4 in HNSCC...
April 2, 2020: Cellular Oncology (Dordrecht)
Gregory D Poore, Evguenia Kopylova, Qiyun Zhu, Carolina Carpenter, Serena Fraraccio, Stephen Wandro, Tomasz Kosciolek, Stefan Janssen, Jessica Metcalf, Se Jin Song, Jad Kanbar, Sandrine Miller-Montgomery, Robert Heaton, Rana Mckay, Sandip Pravin Patel, Austin D Swafford, Rob Knight
Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions1-10 , we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas11 (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer...
March 2020: Nature
Eva Boysen Fynboe Ebert, Tine McCulloch, Karin Holmskov Hansen, Hanne Linnet, Boe Sorensen, Peter Meldgaard
OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are first line treatment choices for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). However, responses vary among patients, therefore good biomarkers predicting better responses are required. EGFR mutations are detected in the blood from patients as circulating tumour DNA (ctDNA). Studies have shown that clearing ctDNA during first line TKI treatment predicts outcomes for first and second generation TKI treatments...
March 19, 2020: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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