{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:20:58Z","timestamp":1773976858210,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Circulating tumour DNA (ctDNA) facilitates longitudinal study of the tumour genome, which, unlike tumour tissue biopsies, globally reflects intratumor and intermetastatis heterogeneity. Despite its costs, next-generation sequencing (NGS) has revolutionised the study of ctDNA, ensuring a more comprehensive and multimodal approach, increasing data collection, and introducing new variables that can be correlated with clinical outcomes. Current NGS strategies can comprise a tumour-informed set of genes or the entire genome and detect a tumour fraction as low as 10\u22125. Despite some conflicting studies, there is evidence that ctDNA levels can predict the worse outcomes of ovarian cancer (OC) in both early and advanced disease. Changes in those levels can also be informative regarding treatment efficacy and tumour recurrence, capable of outperforming CA-125, currently the only universally utilised plasma biomarker in high-grade serous OC (HGSOC). Qualitative evaluation of sequencing shows that increasing copy number alterations and gene variants during treatment may correlate with a worse prognosis in HGSOC. However, following tumour clonality and emerging variants during treatment poses a more unique opportunity to define treatment response, select patients based on their emerging resistance mechanisms, like BRCA secondary mutations, and discover potential targetable variants. Sequencing of tumour biopsies and ctDNA is not always concordant, likely as a result of clonal heterogeneity, which is better captured in the plasma samples than it is in a large number of biopsies. These incoherences may reflect tumour clonality and reveal the acquired alterations that cause treatment resistance. Cell-free DNA methylation profiles can be used to distinguish OC from healthy individuals, and NGS methylation panels have been shown to have excellent diagnostic capabilities. Also, methylation signatures showed promise in explaining treatment responses, including BRCA dysfunction. ctDNA is evolving as a promising new biomarker to track tumour evolution and clonality through the treatment of early and advanced ovarian cancer, with potential applicability in prognostic prediction and treatment selection. While its role in HGSOC paves the way to clinical applicability, its potential interest in other histological subtypes of OC remains unknown.<\/jats:p>","DOI":"10.3390\/biology13020088","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T10:44:24Z","timestamp":1706697864000},"page":"88","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Current Applications and Challenges of Next-Generation Sequencing in Plasma Circulating Tumour DNA of Ovarian Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Ricardo","family":"Roque","sequence":"first","affiliation":[{"name":"Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Portuguese Institute of Oncology of Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-8705","authenticated-orcid":false,"given":"Ilda Patr\u00edcia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-2667","authenticated-orcid":false,"given":"Margarida","family":"Figueiredo-Dias","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Gynecology Department, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Coimbra Academic and Clinical Centre, 3000-370 Coimbra, Portugal"},{"name":"Gynecology Department, Hospital University Centre of Coimbra, 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-7221","authenticated-orcid":false,"given":"Charlie","family":"Gourley","sequence":"additional","affiliation":[{"name":"Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}]},{"given":"Isabel Marques","family":"Carreira","sequence":"additional","affiliation":[{"name":"Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Centre of Investigation on Environment Genetics and Oncobiology (CIMAGO), Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101871","DOI":"10.1016\/j.mcp.2022.101871","article-title":"The Application of Circulating Tumor Cell and Cell-Free DNA Liquid Biopsies in Ovarian Cancer","volume":"66","author":"Jong","year":"2022","journal-title":"Mol. Cell Probes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer Statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"De Leo, A., Santini, D., Ceccarelli, C., Santandrea, G., Palicelli, A., Acquaviva, G., Chiarucci, F., Rosini, F., Ravegnini, G., and Pession, A. (2021). What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors. Diagnostics, 11.","DOI":"10.3390\/diagnostics11040697"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.canlet.2019.10.014","article-title":"Liquid Biopsy in Ovarian Cancer Using Circulating Tumor DNA and Cells: Ready for Prime Time?","volume":"468","author":"Leslie","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/annonc\/mdz062","article-title":"ESMO-ESGO Consensus Conference Recommendations on Ovarian Cancer: Pathology and Molecular Biology, Early and Advanced Stages, Borderline Tumours and Recurrent Disease","volume":"30","author":"Colombo","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Charkhchi, P., Cybulski, C., Gronwald, J., Wong, F.O., Narod, S.A., and Akbari, M.R. (2020). CA125 and Ovarian Cancer: A Comprehensive Review. Cancers, 12.","DOI":"10.3390\/cancers12123730"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13073-017-0500-7","article-title":"The Potential of Circulating Tumor DNA Methylation Analysis for the Early Detection and Management of Ovarian Cancer","volume":"9","author":"Widschwendter","year":"2017","journal-title":"Genome Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s13045-020-00971-6","article-title":"High-Throughput Approaches for Precision Medicine in High-Grade Serous Ovarian Cancer","volume":"13","author":"Meinusha","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13650","DOI":"10.3390\/ijms222413650","article-title":"Role of Circulating Biomarkers in Platinum-Resistant Ovarian Cancer","volume":"22","author":"Carolina","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12943-022-01588-8","article-title":"Potential Clinical Utility of Liquid Biopsies in Ovarian Cancer","volume":"21","author":"Jie","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"943253","DOI":"10.3389\/fonc.2022.943253","article-title":"Circulating Tumor DNA as a Cancer Biomarker: An Overview of Biological Features and Factors That May Impact on CtDNA Analysis","volume":"12","author":"Romero","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fang, Y., Jun, T., Zihao, Z., Chunling, Z., and Yuancai, X. (2021). Circulating Tumor DNA: A Noninvasive Biomarker for Tracking Ovarian Cancer. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-021-00860-8"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s10142-023-01181-2","article-title":"Advances in Application of Circulating Tumor DNA in Ovarian Cancer","volume":"23","author":"Ting","year":"2023","journal-title":"Funct. Integr. Genom."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Parkinson, C.A., Gale, D., Piskorz, A.M., Biggs, H., Hodgkin, C., Addley, H., Freeman, S., Moyle, P., Sala, E., and Sayal, K. (2016). 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. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002198"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1245\/s10434-022-12399-y","article-title":"Circulating Tumor DNA Is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis","volume":"30","author":"Sullivan","year":"2023","journal-title":"Ann. Surg. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1158\/1078-0432.CCR-17-3837","article-title":"The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients","volume":"24","author":"Zill","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1017\/erm.2018.5","article-title":"Potential Clinical Applications of Circulating Cell-Free DNA in Ovarian Cancer Patients","volume":"20","author":"Ana","year":"2018","journal-title":"Expert. Rev. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.jtho.2020.12.011","article-title":"Genotype-Specific Differences in Circulating Tumor DNA Levels in Advanced NSCLC","volume":"16","author":"Lam","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eaat4921","DOI":"10.1126\/scitranslmed.aat4921","article-title":"Enhanced Detection of Circulating Tumor DNA by Fragment Size Analysis","volume":"10","author":"Mouliere","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1038\/s41598-022-05606-z","article-title":"Refined Characterization of Circulating Tumor DNA through Biological Feature Integration","volume":"12","author":"Havell","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12943-022-01551-7","article-title":"A Clinician\u2019s Handbook for Using CtDNA throughout the Patient Journey","volume":"21","author":"Hasenleithner","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Barbosa, A., Pinto, P., Peixoto, A., Guerra, J., Pinto, C., Santos, C., Pinheiro, M., Escudeiro, C., Bartosch, C., and Silva, J. (2020). Gene Panel Tumor Testing in Ovarian Cancer Patients Significantly Increases the Yield of Clinically Actionable Germline Variants beyond BRCA1\/BRCA2. Cancers, 12.","DOI":"10.3390\/cancers12102834"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Singh, R.R. (2022). Target Enrichment Approaches for Next-Generation Sequencing Applications in Oncology. Diagnostics, 12.","DOI":"10.3390\/diagnostics12071539"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Silvia, R.V., Floris, H.G., Ronald, V.M., Corine, M.B., Jean, C.H., Hendrikus, J.D., Winand, N.M.D., Patricia, C.E.G., Ramon, S., and Helena, C.V.D. (2020). TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer. Biomolecules, 10.","DOI":"10.3390\/biom10030415"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nm.3519","article-title":"An Ultrasensitive Method for Quantitating Circulating Tumor DNA with Broad Patient Coverage","volume":"20","author":"Newman","year":"2014","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pereira, E., Camacho-Vanegas, O., Anand, S., Sebra, R., Camacho, S.C., Garnar-Wortzel, L., Nair, N., Moshier, E., Wooten, M., and Uzilov, A. (2015). Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival in Gynecologic Cancers. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145754"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/s41591-020-0915-3","article-title":"Genome-Wide Cell-Free DNA Mutational Integration Enables Ultra-Sensitive Cancer Monitoring","volume":"26","author":"Zviran","year":"2020","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"eaan2415","DOI":"10.1126\/scitranslmed.aan2415","article-title":"Direct Detection of Early-Stage Cancers Using Circulating Tumor DNA","volume":"9","author":"Phallen","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1126\/science.aar3247","article-title":"Detection and Localization of Surgically Resectable Cancers with a Multi-Analyte Blood Test","volume":"359","author":"Cohen","year":"2018","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrg.2017.117","article-title":"Enhancing the Accuracy of Next-Generation Sequencing for Detecting Rare and Subclonal Mutations","volume":"19","author":"Salk","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/s41598-023-27445-2","article-title":"Identification of TP53 Mutations in Circulating Tumour DNA in High Grade Serous Ovarian Carcinoma Using next Generation Sequencing Technologies","volume":"13","author":"Leslie","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Widman, A.J., Shah, M., \u00d8gaard, N., Khamnei, C.C., Frydendahl, A., Deshpande, A., Arora, A., Zhang, M., Halmos, D., and Bass, J. (2022). Machine Learning Guided Signal Enrichment for Ultrasensitive Plasma Tumor Burden Monitoring. bioRxiv.","DOI":"10.1101\/2022.01.17.476508"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nbt.4235","article-title":"A Universal SNP and Small-Indel Variant Caller Using Deep Neural Networks","volume":"36","author":"Poplin","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41467-019-09025-z","article-title":"A Multi-Task Convolutional Deep Neural Network for Variant Calling in Single Molecule Sequencing","volume":"10","author":"Luo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Abdelwahab, O., Belzile, F., and Torkamaneh, D. (2023). Performance Analysis of Conventional and AI-Based Variant Callers Using Short and Long Reads. BMC Bioinform., 24.","DOI":"10.1186\/s12859-023-05596-3"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11205","DOI":"10.1038\/s41598-018-29381-y","article-title":"Massively Parallel Sequencing of Cell-Free DNA in Plasma for Detecting Gynaecological Tumour-Associated Copy Number Alteration","volume":"8","author":"Nakabayashi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"938985","DOI":"10.3389\/fgene.2022.938985","article-title":"Copy Number Variation of Circulating Tumor DNA (CtDNA) Detected Using NIPT in Neoadjuvant Chemotherapy-Treated Ovarian Cancer Patients","volume":"13","author":"Sharbatoghli","year":"2022","journal-title":"Front. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.18.00343","article-title":"Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer","volume":"3","author":"Oikkonen","year":"2019","journal-title":"JCO Precis Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10426","DOI":"10.1038\/s41598-019-47030-w","article-title":"Liquid Biopsy-Based Comprehensive Gene Mutation Profiling for Gynecological Cancer Using CAncer Personalized Profiling by Deep Sequencing","volume":"9","author":"Iwahashi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Noguchi, T., Iwahashi, N., Sakai, K., Matsuda, K., Matsukawa, H., Toujima, S., Nishio, K., and Ino, K. (2020). Comprehensive Gene Mutation Profiling of Circulating Tumor DNA in Ovarian Cancer: Its Pathological and Prognostic Impact. Cancers, 12.","DOI":"10.3390\/cancers12113382"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"TPS3163","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS3163","article-title":"TARGET National: A U.K.-Wide Liquid-Based Molecular Profiling Program to Enhance Recruitment to Early-Phase Trials","volume":"40","author":"Darlington","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/s41591-019-0380-z","article-title":"Utility of CtDNA to Support Patient Selection for Early Phase Clinical Trials: The TARGET Study","volume":"25","author":"Rothwell","year":"2019","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/1878-0261.12791","article-title":"Clinical Implications of Plasma Circulating Tumor DNA in Gynecologic Cancer Patients","volume":"15","author":"Charo","year":"2021","journal-title":"Mol. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13073-021-00897-9","article-title":"Prospective High-Throughput Genome Profiling of Advanced Cancers: Results of the PERMED-01 Clinical Trial","volume":"13","author":"Bertucci","year":"2021","journal-title":"Genome Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"946257","DOI":"10.3389\/fonc.2022.946257","article-title":"Whole-Genome\/Exome Analysis of Circulating Tumor DNA and Comparison to Tumor Genomics from Patients with Heavily Pre-Treated Ovarian Cancer: Subset Analysis of the PERMED-01 Trial","volume":"12","author":"Renaud","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1158\/2159-8290.CD-18-0715","article-title":"BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma","volume":"9","author":"Kevin","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1158\/1078-0432.CCR-22-3715","article-title":"Investigation of PARP Inhibitor Resistance Based on Serially Collected Circulating Tumor DNA in Patients With BRCA-Mutated Ovarian Cancer","volume":"29","author":"Kim","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6708","DOI":"10.1158\/1078-0432.CCR-17-0544","article-title":"Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer","volume":"23","author":"Weigelt","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1200\/JCO.2016.70.4627","article-title":"Reversion of BRCA1\/2 Germline Mutations Detected in Circulating Tumor DNA from Patients with High-Grade Serous Ovarian Cancer","volume":"35","author":"Christie","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1158\/2159-8290.CD-17-0419","article-title":"Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma","volume":"7","author":"Kondrashova","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1158\/1078-0432.CCR-20-3345","article-title":"Genome-Wide Copy-Number Alterations in Circulating Tumor DNA as a Novel Biomarker for Patients with High-Grade Serous Ovarian Cancer","volume":"27","author":"Paracchini","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ygyno.2022.09.004","article-title":"Circulating Tumor DNA Monitoring for Early Recurrence Detection in Epithelial Ovarian Cancer","volume":"167","author":"Hou","year":"2022","journal-title":"Gynecol. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Chao, A., Chen, S.J., Chen, H.C., Tan, K.T., Hsiao, W., Jung, S.M., Yang, L.-Y., Huang, K.-G., Chou, H.-H., and Huang, H.-J. (2022). Mutations in Circulating Tumor DNA Detected in the Postoperative Period Predict Poor Survival in Patients with Ovarian Cancer. Biomed. J., 46.","DOI":"10.1016\/j.bj.2022.09.004"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhu, J.W., Wong, F., Szymiczek, A., Ene, G.E.V., Zhang, S., May, T., Narod, S.A., Kotsopoulos, J., and Akbari, M.R. (2023). Evaluating the Utility of CtDNA in Detecting Residual Cancer and Predicting Recurrence in Patients with Serous Ovarian Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814388"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Marian, C.A., Fernando, L.A.F., Alayne, M.T., Barros, L.A.D.R., Lopes, A., Silva, L.C.F.F., Luz, A.S., Cruz, F.J.S.M., and Del Giglio, A. (2020). Increased Circulating Tumor DNA as a Noninvasive Biomarker of Early Treatment Response in Patients with Metastatic Ovarian Carcinoma: A Pilot Study. Tumour Biol., 42.","DOI":"10.1177\/1010428320919198"},{"key":"ref_56","first-page":"1219","article-title":"Evaluation of Circulating Tumor DNA in Patients with Ovarian Cancer Harboring Somatic PIK3CA or KRAS Mutations","volume":"52","author":"Alves","year":"2020","journal-title":"Cancer Res. Treat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1016\/j.ejca.2014.06.022","article-title":"Prognostic Importance of Cell-Free DNA in Chemotherapy Resistant Ovarian Cancer Treated with Bevacizumab","volume":"50","author":"Steffensen","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.3390\/cancers14153697","article-title":"Targeted Mutational Analysis of Circulating Tumor DNA to Decipher Temporal Heterogeneity of High-Grade Serous Ovarian Cancer","volume":"14","author":"Lara","year":"2022","journal-title":"Cancers"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"779","DOI":"10.4143\/crt.2019.700","article-title":"Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer","volume":"52","author":"Han","year":"2020","journal-title":"Cancer Res. Treat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.3390\/cancers13102386","article-title":"Liquid Biopsy in the Clinical Management of High-Grade Serous Epithelial Ovarian Cancer-Current Use and Future Opportunities","volume":"13","author":"Lara","year":"2021","journal-title":"Cancers"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"754094","DOI":"10.3389\/fonc.2021.754094","article-title":"Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in CtDNA From Ovarian Cancer Patients","volume":"11","author":"Barbosa","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2100289","DOI":"10.1200\/PO.21.00289","article-title":"Genomic Landscape of Advanced Solid Tumors in Circulating Tumor DNA and Correlation With Tissue Sequencing: A Single Institution\u2019s Experience","volume":"6","author":"Gerratana","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13148-023-01440-w","article-title":"Early Diagnosis of Ovarian Cancer Based on Methylation Profiles in Peripheral Blood Cell-Free DNA: A Systematic Review","volume":"15","author":"Simone","year":"2023","journal-title":"Clin. Epigenet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.31557\/APJCP.2019.20.10.3001","article-title":"Aberrant Promoter Hypermethylation of RASSF1a and BRCA1 in Circulating Cell-Free Tumor DNA Serves as a Biomarker of Ovarian Carcinoma","volume":"20","author":"Sandeep","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1158\/1940-6207.CAPR-19-0184","article-title":"Reducing Ovarian Cancer Mortality Through Early Detection: Approaches Using Circulating Biomarkers","volume":"13","author":"Trinidad","year":"2020","journal-title":"Cancer Prev. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ygyno.2010.09.019","article-title":"Distinctive DNA Methylation Patterns of Cell-Free Plasma DNA in Women with Malignant Ovarian Tumors","volume":"120","author":"Liggett","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1002\/ijc.32984","article-title":"Detection of Aberrant Methylation of HOXA9 and HIC1 through Multiplex MethyLight Assay in Serum DNA for the Early Detection of Epithelial Ovarian Cancer","volume":"147","author":"Alka","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.annonc.2020.02.011","article-title":"Sensitive and Specific Multi-Cancer Detection and Localization Using Methylation Signatures in Cell-Free DNA","volume":"31","author":"Liu","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.3390\/ijms20174119","article-title":"Aberrant Methylation Status of Tumour Suppressor Genes in Ovarian Cancer Tissue and Paired Plasma Samples","volume":"20","author":"Dana","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1093\/annonc\/mdt370","article-title":"Association of Somatic DNA Methylation Variability with Progression-Free Survival and Toxicity in Ovarian Cancer Patients","volume":"24","author":"Flanagan","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1158\/1078-0432.CCR-16-1754","article-title":"Platinum-Based Chemotherapy Induces Methylation Changes in Blood DNA Associated with Overall Survival in Patients with Ovarian Cancer","volume":"23","author":"Flanagan","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Liang, L., Zhang, Y., Li, C., Liao, Y., Wang, G., Xu, J., Li, Y., Yuan, G., Sun, Y., and Zhang, R. (2022). Plasma CfDNA Methylation Markers for the Detection and Prognosis of Ovarian Cancer. EBioMedicine, 83.","DOI":"10.1016\/j.ebiom.2022.104222"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Tomar, T., Alkema, N.G., Schreuder, L., Meersma, G.J., de Meyer, T., van Criekinge, W., Klip, H.G., Fiegl, H., van Nieuwenhuysen, E., and Vergote, I. (2017). Methylome Analysis of Extreme Chemoresponsive Patients Identifies Novel Markers of Platinum Sensitivity in High-Grade Serous Ovarian Cancer. BMC Med., 15.","DOI":"10.1186\/s12916-017-0870-0"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Houshdaran, S., Hawley, S., Palmer, C., Campan, M., Olsen, M.N., Ventura, A.P., Knudsen, B.S., Drescher, C.W., Urban, N.D., and Brown, P.O. (2010). DNA Methylation Profiles of Ovarian Epithelial Carcinoma Tumors and Cell Lines. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009359"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Rodger, E.J., Almomani, S.N., Ludgate, J.L., Stockwell, P.A., Baguley, B.C., Eccles, M.R., and Chatterjee, A. (2021). Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines. Cancers, 13.","DOI":"10.3390\/cancers13092123"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ohnmacht, A.J., Rajamani, A., Avar, G., Kutkaite, G., Gon\u00e7alves, E., Saur, D., and Menden, M.P. (2023). The Pharmacoepigenomic Landscape of Cancer Cell Lines Reveals the Epigenetic Component of Drug Sensitivity. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05198-y"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1038\/bjc.2014.104","article-title":"Breast Cancer Metastasis Suppressor-1 Promoter Methylation in Cell-Free DNA Provides Prognostic Information in Non-Small Cell Lung Cancer","volume":"110","author":"Balgkouranidou","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.semcancer.2021.08.005","article-title":"Platinum-Resistant Ovarian Cancer: From Drug Resistance Mechanisms to Liquid Biopsy-Based Biomarkers for Disease Management","volume":"77","author":"Khan","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1002\/1878-0261.13108","article-title":"BRCA1 Promoter Hypermethylation on Circulating Tumor DNA Correlates with Improved Survival of Patients with Ovarian Cancer","volume":"15","author":"Maha","year":"2021","journal-title":"Mol. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"643","DOI":"10.5468\/ogs.20033","article-title":"Prevalence of Tumor BRCA1 and BRCA2 Dysfunction in Unselected Patients with Ovarian Cancer","volume":"63","author":"Kalachand","year":"2020","journal-title":"Obs. Gynecol. Sci."},{"key":"ref_81","first-page":"3970","article-title":"Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma","volume":"28","author":"Olga","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ejca.2019.11.012","article-title":"Circulating HOXA9-Methylated Tumour DNA: A Novel Biomarker of Response to Poly (ADP-Ribose) Polymerase Inhibition in BRCA-Mutated Epithelial Ovarian Cancer","volume":"125","author":"Maria","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"a004648","DOI":"10.1101\/mcs.a004648","article-title":"Rapid Development and Use of Patient-Specific CtDNA Biomarkers to Avoid a \u201cRash Decision\u201d in an Ovarian Cancer Patient","volume":"5","author":"Pandya","year":"2019","journal-title":"Mol. Case Stud."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/2\/88\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:52:08Z","timestamp":1760104328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/2\/88"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":83,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["biology13020088"],"URL":"https:\/\/doi.org\/10.3390\/biology13020088","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,31]]}}}