Review
Medicine, General & Internal
Spencer C. Ding, Y. M. Dennis Lo
Summary: Cell-free DNA (cfDNA) has revolutionized the development of noninvasive prenatal testing, cancer liquid biopsy, and transplantation monitoring. The study of cfDNA fragmentation patterns, known as 'fragmentomics,' has provided valuable information about the tissue of origin of cfDNA molecules. Recent advancements in understanding cfDNA fragmentation have led to the discovery of fragmentomic markers with potential clinical applications.
Article
Multidisciplinary Sciences
Qing Zhou, Guannan Kang, Peiyong Jiang, Rong Qiao, W. K. Jacky Lam, Stephanie C. Y. Yu, Mary-Jane L. Ma, Lu Ji, Suk Hang Cheng, Wanxia Gai, Wenlei Peng, Huimin Shang, Rebecca W. Y. Chan, Stephen L. Chan, Grace L. H. Wong, Linda T. Hiraki, Stefano Volpi, Vincent W. S. Wong, John Wong, Rossa W. K. Chiu, K. C. Allen Chan, Y. M. Dennis Lo
Summary: The fragmentation patterns of cell-free DNA can be used to predict CpG methylation and have important implications for noninvasive prenatal diagnosis, cancer, and organ transplantation assessment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Mohammad Amin Kerachian, Marjan Azghandi, Sina Mozaffari-Jovin, Alain R. Thierry
Summary: Methylation analysis of circulating cell-free DNA (cirDNA) has significant potential in advancing cancer detection, prognosis, and treatment, as well as genetic disorders. The choice of pre-analytical variables can impact cirDNA methylation identification, while different techniques yield varying results. Despite efforts to simplify methylation analysis with new technologies, the process remains complex and lacks a standard method for pre-analytical processing of methylated cirDNA.
CLINICAL EPIGENETICS
(2021)
Review
Biochemistry & Molecular Biology
Caterina Gianni, Michela Palleschi, Filippo Merloni, Giandomenico Di Menna, Marianna Sirico, Samanta Sarti, Alessandra Virga, Paola Ulivi, Lorenzo Cecconetto, Marita Mariotti, Ugo De Giorgi
Summary: This review focuses on the available research on circulating cell-free DNA integrity as a biomarker for diagnosis, prognosis, and treatment response in breast cancer, highlighting new perspectives and critical issues for future applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Ilana Fox-Fisher, Sheina Piyanzin, Bracha Lea Ochana, Agnes Klochendler, Judith Magenheim, Ayelet Peretz, Netanel Loyfer, Joshua Moss, Daniel Cohen, Yaron Drori, Nehemya Friedman, Michal Mandelboim, Marc E. Rothenberg, Julie M. Caldwell, Mark Rochman, Arash Jamshidi, Gordon Cann, David Lavi, Tommy Kaplan, Benjamin Glaser, Ruth Shemer, Yuval Dor
Summary: The immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) can be used for studying human immune cell dynamics and provide a novel biomarker for monitoring immune responses to physiological and pathological processes.
Article
Oncology
Shuxin Zhang, Jun Zhang, Xinlei Hu, Senlin Yin, Yunbo Yuan, Lin Xia, Feng Cao, Xiaoqin Yan, Ziyue Yan, Qing Mao, Dan Xie, Yanhui Liu
Summary: A liquid biopsy method based on sequencing of plasma cfDNA fragments carrying 5hmC has been developed, which can detect brain gliomas and predict the aggressiveness of the tumors.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Genetics & Heredity
Megan E. Barefoot, Netanel Loyfer, Amber J. Kiliti, A. Patrick McDeed, Tommy Kaplan, Anton Wellstein
Summary: Traditional tissue biopsies for cancer diagnostics have limitations such as invasiveness and sampling inaccuracies, while liquid biopsies offer a complementary approach to detect dynamic changes in specific cell populations. Changes in cellular origins of cfDNA can reveal altered tissue homeostasis, including cancer invasion and metastasis, as well as treatment responses.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Lars Sivars, Kristina Hellman, Ylva Crona Guterstam, Stefan Holzhauser, Magnus Nordenskjold, Henrik Falconer, Kolbrun Palsdottir, Emma Tham
Summary: This study aimed to analyze the detectability of cell-free human papillomavirus DNA (ctHPV DNA) in patients with cervical cancer or pre-malignant lesions and its correlation with patient and tumor characteristics and outcome. The results showed a high proportion of ctHPV DNA detection in patients with locally advanced cervical cancer, and its levels were correlated with disease staging. Furthermore, the presence of ctHPV DNA was associated with worse progression-free survival in patients.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Medicine, General & Internal
Preawwalee Wintachai, Jing Quan Lim, Anchalee Techasen, Worachart Lert-Itthiporn, Sarinya Kongpetch, Watcharin Loilome, Jarin Chindaprasirt, Attapol Titapun, Nisana Namwat, Narong Khuntikeo, Apinya Jusakul
Summary: The study found that cfDNA levels were significantly higher in CCA compared to benign biliary disease and normal controls. cfDNA levels showed superior diagnostic efficacy in discriminating CCA from healthy controls and BBD.
Article
Oncology
Iben Lyskjaer, Neesha Kara, Solange De Noon, Christopher Davies, Ana Maia Rocha, Anna-Christina Strobl, Inga Usher, Craig Gerrand, Sandra J. Strauss, Daniel Schrimpf, Andreas von Deimling, Stephan Beck, Adrienne M. Flanagan
Summary: The study aimed to discover and validate methylation-based biomarkers to detect plasma circulating tumor DNA (ctDNA) in osteosarcoma (OS) patients and explore their utility as prognostic markers. The findings showed the potential of mutation-independent methylation-based ctDNA assays for OS and laid the foundation for further multi-institutional collaborative studies on plasma-derived biomarkers in the management of OS.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Multidisciplinary Sciences
Y. M. Dennis Lo, Diana S. C. Han, Peiyong Jiang, Rossa W. K. Chiu
Summary: Liquid biopsies, which analyze cell-free DNA in blood plasma, are utilized for noninvasive prenatal testing, oncology, and organ transplant monitoring. The physical and molecular features of cell-free DNA fragments, along with their distribution over the genome, contain information about their tissues of origin. These features, including DNA methylation patterns and nucleosomal organization, hold promise for noninvasive detection of tissue-specific pathologies with a variety of clinical applications.
Article
Biochemistry & Molecular Biology
Vassilis M. Papadakis, Christina Cheimonidi, Maria Panagopoulou, Makrina Karaglani, Paraskevi Apalaki, Klytaimnistra Katsara, George Kenanakis, Theodosis Theodosiou, Theodoros C. Constantinidis, Kalliopi Stratigi, Ekaterini Chatzaki
Summary: In this study, Raman spectroscopy was used to analyze the biomolecular characteristics of cell-free DNA (ccfDNA) in the blood of individuals with different health conditions. The study found distinct spectral patterns in ccfDNA from breast cancer patients undergoing neoadjuvant therapy, as well as some differences in the biomolecular fingerprints of ccfDNA from healthy, prediabetic, and diabetic males. The analysis also confirmed that ccfDNA mirrors its cellular origin. Overall, the study highlights the potential of Raman spectroscopy as a new approach for liquid biopsy diagnostics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Arash Jamshidi, Minetta C. Liu, Eric A. Klein, Oliver Venin, Earl Hubbell, John F. Beausang, Samuel Gross, Collin Melton, Alexander P. Fields, Qinwen Liu, Nan Zhang, Eric T. Fung, Kathryn N. Kurtzman, Hamed Amini, Craig Betts, Daniel Civello, Peter Freese, Robert Calef, Konstantin Davydov, Saniya Fayzullina, Chenlu Hou, Roger Jiang, Byoungsok Jung, Susan Tang, Vasiliki Demas, Joshua Newman, Onur Sakarya, Eric Scott, Archana Shenoy, Seyedmehdi Shojaee, Kristan K. Steffen, Virgil Nicula, Tom C. Chien, Siddhartha Bagaria, Nathan Hunkapiller, Mohini Desai, Zhao Dong, Donald A. Richards, Timothy J. Yeatman, Allen L. Cohn, David D. Thiel, Donald A. Berry, Mohan K. Tummala, Kristi MCIntyre, Mikkael A. Sekeres, Alan Bryce, Alexander M. Aravanis, Michael V. Seiden, Charles Swanton
Summary: In this study, we evaluated several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test and identified the most promising method, which is the use of whole-genome methylation feature. cTAF is an important predictor of classifier performance and more closely reflects tumor biology.
Review
Biochemistry & Molecular Biology
Ting Qi, Min Pan, Huajuan Shi, Liangying Wang, Yunfei Bai, Qinyu Ge
Summary: Cell-free DNA molecules are released into the plasma and carry genetic and epigenetic information. Enriching cfDNA fragments with diagnostic value is challenging, but recent evidence suggests that cfDNA fragmentomics can serve as a promising biomarker without distinguishing fragment sources. Additionally, cfDNA fragmentomics can identify tissue origins by inferring epigenetic information. Understanding the fragmentomics of plasma cfDNA can shed light on its origin and fragmentation mechanisms, enhancing its potential as a molecular diagnostic tool. In this review, we discuss cfDNA fragment characteristics, its potential applications, and methods for deducing tissue of origin by cfDNA fragmentomics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Yaping Liu
Summary: Epigenetic mechanisms are essential in gene regulation, and circulating cell-free DNA (cfDNA) in peripheral blood provides a non-invasive way to monitor the genomes of inaccessible tissues. The fragment patterns of plasma cfDNA reflect gene regulation status and have the potential to identify tissue origin. Studies in this area pave the way for non-invasive monitoring of gene regulatory dynamics in both peripheral immune cells and diseased tissues.
BRITISH JOURNAL OF CANCER
(2022)
Review
Oncology
Richard Mair, Florent Mouliere
Summary: Over the past 20 years, survival rates for glioma patients have shown minimal improvement, with detection and monitoring relying primarily on imaging technologies. Liquid biopsy may offer a more convenient clinical scenario for monitoring treatment response, but technical and biological issues related to low concentrations of tumor-derived DNA in the bloodstream of glioma patients are hindering its full potential.
BRITISH JOURNAL OF CANCER
(2022)
Review
Emergency Medicine
Matthew Henry Vincent Byrne, James Ashcroft, Laith Alexander, Jonathan C. M. Wan, Anna Harvey
Summary: The study found that a high number of students are willing to volunteer during disasters, but they may lack proper preparation due to a low overall knowledge level. The lack of disaster education in medical schools highlights the need to develop infrastructure to ensure that students are adequately prepared for future disasters.
EMERGENCY MEDICINE JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Irena Hudecova, Christopher G. Smith, Robert Hansel-Hertsch, Chandra S. Chilamakuri, James A. Morris, Aadhitthya Vijayaraghavan, Katrin Heider, Dineika Chandrananda, Wendy N. Cooper, Davina Gale, Javier Garcia-Corbacho, Simon Pacey, Richard D. Baird, Nitzan Rosenfeld, Florent Mouliere
Summary: Current evidence suggests that plasma cell-free DNA (cfDNA) is fragmented around 166 bp. A novel population of ultrashort plasma cfDNA fragments centered at 50 bp was discovered, showing higher relative abundance in healthy individuals compared to cancer patients. These ultrashort cfDNA fragments map to accessible chromatin regions of blood cells, particularly in promoter regions with the potential for G-quadruplex DNA secondary structures. G4-positive promoter chromatin accessibility is significantly enriched in ultrashort plasma cfDNA fragments from healthy individuals relative to cancer patients.
Article
Medical Laboratory Technology
Ymke van der Pol, Norbert Moldovan, Sandra Verkuijlen, Jip Ramaker, Dries Boers, Wendy Onstenk, Johan de Rooij, Idris Bahce, D. Michiel Pegtel, Florent Mouliere
Summary: This study analyzed the impact of collection tube, plasma processing time, and physiology on cfDNA, and found that different collection tubes and processing times did not affect the fragment sizes of cfDNA, but could impact the genome-wide fragmentation patterns and fragment-end sequences. Additionally, physiological conditions minimally influenced the outcome of cfDNA fragmentomic methods.
CLINICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Filipe Correia Martins, Dominique-Laurent Couturier, Ines de Santiago, Carolin Margarethe Sauer, Maria Vias, Mihaela Angelova, Deborah Sanders, Anna Piskorz, James Hall, Karen Hosking, Anumithra Amirthanayagam, Sabina Cosulich, Larissa Carnevalli, Barry Davies, Thomas B. K. Watkins, Ionut G. Funingana, Helen Bolton, Krishnayan Haldar, John Latimer, Peter Baldwin, Robin Crawford, Matthew Eldridge, Bristi Basu, Mercedes Jimenez-Linan, Andrew W. Mcpherson, Nicholas McGranahan, Kevin Litchfield, Sohrab P. Shah, Iain McNeish, Carlos Caldas, Gerard Evan, Charles Swanton, James D. Brenton
Summary: Identification of clonal somatic copy number alterations in cancer genes can guide precision medicine for high-grade serous ovarian carcinoma.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Yasmin A. Civil, Arlene L. Oei, Katya M. Duvivier, Nina Bijker, Philip Meijnen, Lorraine Donkers, Sonja Verheijen, Zdenko van Kesteren, Miguel A. Palacios, Laura J. Schijf, Ellis Barbe, Inge R. H. M. Konings, C. Willemien Menke van der Houven van Oordt, Paulien G. Westhoff, Hanneke J. M. Meijer, Gwen M. P. Diepenhorst, Victor Thijssen, Florent Mouliere, Berend J. Slotman, Susanne van der Velde, H. J. G. Desiree van den Bongard
Summary: This study aims to assess the pathological complete response (pCR) rate one year after MR-guided single-dose pre-operative partial breast irradiation (PBI) in low-risk breast cancer patients. MRI and biomarkers will be used to monitor treatment response and predict pCR.
Article
Medicine, Research & Experimental
Angela Santonja, Wendy N. Cooper, Matthew D. Eldridge, Paul A. W. Edwards, James A. Morris, Abigail R. Edwards, Hui Zhao, Katrin Heider, Dominique-Laurent Couturier, Aadhitthya Vijayaraghavan, Paulius Mennea, Emma-Jane Ditter, Christopher G. Smith, Chris Boursnell, Raquel Manzano Garcia, Oscar M. Rueda, Emma Beddowes, Heather Biggs, Stephen-John Sammut, Nitzan Rosenfeld, Carlos Caldas, Jean E. Abraham, Davina Gale
Summary: Analysis of different methods for detecting circulating tumor DNA (ctDNA) in breast cancer patients' plasma samples showed that the dynamics and allele fractions were consistent across assays. Tumor-informed assays had the highest sensitivity for detecting ctDNA at low concentrations, while hybrid capture sequencing at high depth was the most sensitive assay overall.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Philip Smith, Thomas Bradley, Lena Morrill Gavarro, Teodora Goranova, Darren P. Ennis, Hasan B. Mirza, Dilrini De Silva, Anna M. Piskorz, Carolyn Sauer, Sarwah Al-Khalidi, Ionat-Gabriel Funingana, Marika A. V. Reinius, Gaia Giannone, Liz-Anne Lewsley, Jamie Stobo, John McQueen, Gareth Bryson, Matthew Eldridge, R. M. Glasspool, C. Gourley, R. Kennedy, G. Hall, R. Edmondson, A. Clamp, S. Sundar, A. Walter, M. Hall, H. Gabra, C. Fotopoulou, E. Brockbank, A. Montes, M. Lockley, Geoff Macintyre, Florian Markowetz, James D. Brenton, Iain A. McNeish
Summary: Treatment resistance is common in ovarian high grade serous carcinoma, often leading to relapse. Here, the authors leverage shallow whole genome and panel sequencing of 276 patients with available diagnostic and relapse samples and show high concordance of copy number and mutation status.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Mireia Crispin-Ortuzar, Ramona Woitek, Marika A. V. Reinius, Elizabeth Moore, Lucian Beer, Vlad Bura, Leonardo Rundo, Cathal McCague, Stephan Ursprung, Lorena Escudero Sanchez, Paula Martin-Gonzalez, Florent Mouliere, Dineika Chandrananda, James Morris, Teodora Goranova, Anna M. Piskorz, Naveena Singh, Anju Sahdev, Roxana Pintican, Marta Zerunian, Nitzan Rosenfeld, Helen Addley, Mercedes Jimenez-Linan, Florian Markowetz, Evis Sala, James D. Brenton
Summary: High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease with difficulties in predicting response to chemotherapy. This study presents a framework that integrates baseline clinical data, blood-based markers, and radiomic biomarkers to predict the response of patients to chemotherapy. The results show that incorporating radiomics data into the model significantly improves prediction accuracy.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Ymke van der Pol, Norbert Moldovan, Jip Ramaker, Sanne Bootsma, Kristiaan J. Lenos, Louis Vermeulen, Shahneen Sandhu, Idris Bahce, D. Michiel Pegtel, Stephen Q. Wong, Sarah-Jane Dawson, Dineika Chandrananda, Florent Mouliere
Summary: This study found that the level of mtDNA is increased in plasma samples of patients with certain types of cancer, such as cholangiocarcinoma, colorectal, liver, pancreatic, or prostate cancer. By combining mtDNA and copy number analysis, a predictive model can improve the detection of cancer in liquid biopsies.
Article
Medicine, Research & Experimental
Ymke van Der Pol, Normastuti Adhini Tantyo, Nils Evander, Anouk E. Hentschel, Birgit M. M. Wever, Jip Ramaker, Sanne Bootsma, Marieke F. Fransen, Kristiaan J. Lenos, Louis Vermeulen, Famke L. Schneiders, Idris Bahce, Jakko A. Nieuwenhuijzen, Renske D. M. Steenbergen, D. Michiel Pegtel, Norbert Moldovan, Florent Mouliere
Summary: This study demonstrates the use of Oxford Nanopore Technologies (ONT) sequencing to obtain genomic and fragmentomic data from liquid biopsies. The results show that copy number aberrations and cfDNA fragmentation patterns can be determined in less than 24 hours. Furthermore, ONT sequencing allows analysis of previously understudied cfDNA populations.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Philip Smith, Thomas Bradley, Lena Morrill Gavarro, Teodora Goranova, Darren P. Ennis, Hasan B. Mirza, Dilrini De Silva, Anna M. Piskorz, Carolin M. Sauer, Sarwah Al-Khalidi, Ionut-Gabriel Funingana, Marika A. V. Reinius, Gaia Giannone, Liz-Anne Lewsley, Jamie Stobo, John Mcqueen, Gareth Bryson, R. M. Glasspool, C. Gourley, R. Kennedy, G. Hall, R. Edmondson, A. Clamp, S. Sundar, A. Walter, M. Hall, H. Gabra, C. Fotopoulou, E. Brockbank, A. Montes, M. Lockley, Geoff Macintyre, Florian Markowetz, Matthew Eldridge, James D. Brenton, Iain A. Mcneish
Summary: This study investigates the drivers of recurrence and resistance in ovarian high grade serous carcinoma and finds a high concordance between diagnosis and relapse, suggesting that acquired chemotherapy resistance does not select for common copy number drivers.
NATURE COMMUNICATIONS
(2023)