bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–02–01
six papers selected by
Lara Paracchini, Humanitas Research
  1. The cervico-vaginal DNA methylation WID-qEC test: An epigenetic marker associated with ovarian cancer in the absence of endometrial and cervical cancer.
  2. Genome-wide extraction of differentially methylated DNA regions using adapter-anchored proximity primers.
  3. Epigenetic Instability Based Metrics in Cell-Free DNA for Early Cancer Detection.
  4. Non-invasive screening in hereditary cancer: a randomized controlled trial to test cell-free DNA-based early detection in the CHARM consortium.
  5. Ultrasensitive ctDNA monitoring reveals early predictors of immunotherapy response in advanced cancer.
  6. Emerging Role of ctDNA Fragmentomics and Epigenetic Signatures in the Early Detection, Minimal Residual Disease Assessment, and Precision Monitoring of Renal Cell Carcinoma.
  1. Int J Cancer. 2026 Jan 29.
    The cervico-vaginal DNA methylation WID-qEC test: An epigenetic marker associated with ovarian cancer in the absence of endometrial and cervical cancer.
    Elisa Redl, Chiara Herzog, Charlotte Vavourakis, James Barrett, Allison Jones, Iona Evans, Daniel Reisel, Ranjit Manchanda, Line Bjørge, Michal Zikan, David Cibula, Twana Alkasalias, Angelique Flöter Rådestad, Kristina Gemzell-Danielsson, Louis Dubeau, Nicola MacDonald, Davor Jurkovic, Nora Pashayan, Martin Widschwendter.
      The DNA methylation-based WID-qEC test, applied to cervico-vaginal samples, has been validated for the accurate detection of endometrial and cervical cancers. However, a small proportion of women test positive despite the absence of these cancers. The aim of this study was to explore the biological and clinical characteristics associated with such WID-qEC-positive cases to inform potential follow-up strategies. We analyzed 1269 cervico-vaginal samples from women without endometrial or cervical cancer, including healthy controls (n = 624), women with benign gynecological conditions (n = 324), and ovarian cancer cases (n = 321). Of the 80 WID-qEC-positive results, 43 (54%) were from women with ovarian cancer. WID-qEC positivity was associated with the presence of ovarian cancer (adjusted odds ratio [OR] 2.93; 95% CI 1.75-4.95) and with a higher number of lifetime ovulatory cycles (adjusted OR 2.67; 95% CI 1.06-7.50), a known ovarian cancer risk factor. Both associations were independent of age, menopausal status, hormone replacement therapy usage, or family history of breast or ovarian cancer. Our findings suggest that in the absence of endometrial or cervical cancer, WID-qEC positivity may indicate an elevated risk or presence of ovarian cancer. While the standalone positive predictive value (PPV) for ovarian cancer detection remains low in the general population, we outline how WID-qEC could be used in a two-step triage approach. In women presenting with abnormal bleeding, combining WID-qEC positivity with a highly specific plasma-based cell-free DNA methylation test (e.g., with 60%-80% sensitivity and ~98.4% specificity) could theoretically yield a PPV of around 30%-40%. This hypothetical modeling is intended solely to illustrate how WID-qEC positivity might inform future triage research, rather than to propose a clinical diagnostic algorithm.
    Keywords:  DNA methylation; cervico‐vaginal sample; WID‐qEC test; ovarian cancer
    DOI:  https://doi.org/10.1002/ijc.70354
  2. Nucleic Acids Res. 2026 Jan 22. pii: gkag056. [Epub ahead of print]54(3):
    Genome-wide extraction of differentially methylated DNA regions using adapter-anchored proximity primers.
    Farzaneh Darbeheshti, Hayet Radia Zeggar, Hamzeh Salmani, Yibin Liu, Eleni Thanou, Athina Markou, Giannis Vatsellas, Samira Ghazali, Ruolin Liu, Evi Lianidou, Viktor A Adalsteinsson, G Mike Makrigiorgos.
      The epigenetic deregulation of CpG islands (CGIs) plays a crucial role in cancer initiation and progression. CGIs comprise 1%-2% of the human genome and are rich in differentially methylated regions (DMRs) that can serve as biomarkers in clinical samples and liquid biopsies. Focusing epigenetic sequencing on CpG-rich regions, including CGIs, while avoiding non-informative sequences, offers an efficient and sensitive approach for cancer detection and monitoring, especially in samples with excess normal DNA. To this end, we developed adaptor-anchored methylation amplification via proximity primers (aMAPPs), a versatile PCR-based enrichment method. Proximity primers (PPs) are specially designed primers that amplify either methylated or unmethylated proximal CpGs, depending on the selected methylation conversion method. aMAPP achieves high-coverage of genome-wide CGIs and detects numerous DMRs in tumor samples compared to adjacent normal tissue using ultra-low depth sequencing (∼300 000 reads). aMAPP enables detection of aberrant methylation down to 0.01% allelic frequency in tumor DNA dilutions and cell-free DNA, requires only picogram DNA input, and can be adapted to enrich either small panels of cancer-specific DMRs or large genomic-fractions including >90% of genomic CGIs. Overall, aMAPP provides a simple, cost-effective, and highly sensitive strategy for capturing the epigenetic footprint of genome-wide CpGs and identifying aberrant methylation events.
    DOI:  https://doi.org/10.1093/nar/gkag056
  3. Clin Cancer Res. 2026 Jan 27.
    Epigenetic Instability Based Metrics in Cell-Free DNA for Early Cancer Detection.
    Sara-Jayne Thursby, Zhicheng Jin, Jacob Blum, Andrei Gurau, Michaël Noë, Robert B Scharpf, Victor E Velculescu, Leslie Cope, Malcolm Brock, Stephen Baylin, Thomas Pisanic, Hariharan Easwaran.
       PURPOSE: Cancers present significant DNA methylation changes, which arise in a stochastic manner, marked by extensive epigenetic variation, indicative of high epigenetic instability. We aimed to evaluate the utility of epigenetic instability for cell-free DNA (cfDNA)-based cancer detection.
    EXPERIMENTAL DESIGN: Through analysis of cancer DNA methylation datasets (n=2,084), we identified a set of 269 CGI regions that robustly captures this instability in a cancer-specific manner. We developed metrics to measure this epigenetic instability, termed the Epigenetic Instability Index (EII), for cancer screening via cfDNA methylation.
    RESULTS: Machine learning classifiers employing the EII of these 269 regions efficiently identified breast and lung cancer from cfDNA, differentiating even stage IA LUAD with ~81% sensitivity and early-stage breast cancer with ~68% sensitivity, both at 95% specificity.
    CONCLUSION: Our studies demonstrate that quantifying epigenetic instability is a novel, capable approach to distinguishing cancer from normal cases using cfDNA, performing better than standard approaches using absolute methylation changes. The epigenetic instability-based approaches for cancer detection developed here, along with their validation in independent datasets, support further development and the potential for future clinical application of these strategies in cancer screening.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-25-3384
  4. Eur J Hum Genet. 2026 Jan 29.
    Non-invasive screening in hereditary cancer: a randomized controlled trial to test cell-free DNA-based early detection in the CHARM consortium.
    Kirsten M Farncombe, Julia A Sobotka, Melyssa Aronson, Mark Basik, Yvonne Bombard, Leslie Born, Rona Cheifetz, Marc Clausen, Natalie Coburn, Lesa Dawson, Andrea S Doria, Khaled Y Elbanna, Holly Etchegary, William D Foulkes, Chiquita Hessels, Angela Hyde, Karineh Kazazian, Adam Kinnaird, C Anne Koch, Stephane Laframboise, Jordan Lerner-Ellis, Stephanie Lheureux, David Malkin, Ur Metser, Lynette S Penney, Sarah Ridd, Kasmintan A Schrader, Teresa Tiano, Alicia A Tone, Patrick Veit-Haibach, Stephanie Wong, Wei Xu, Trevor J Pugh, Raymond H Kim.
      Individuals with hereditary cancer syndromes are born with germline genetic variants that significantly increase their lifetime risk of developing multiple cancers. Cancer rates and overall mortality can be reduced with intensive surveillance to facilitate early cancer detection. However, participating in diagnostic imaging and endoscopy surveillance programs is often time-consuming, overwhelming, inconvenient, and anxiety-inducing. To improve this, multi-cancer early detection tests are being developed using cell-free DNA (cfDNA) sequencing analysis to detect cancers with more sensitivity than conventional screening methods. Our community (the CHARM consortium: Cell-free DNA in Hereditary And high-Risk Malignancies) has been exploring the use of cfDNA sequencing in hereditary cancer, and has launched the CHARM2 prospective randomized controlled trial, which is enrolling 1000 participants with Hereditary Breast and Ovarian Cancer, Lynch syndrome, Li-Fraumeni syndrome, Neurofibromatosis type 1 and Hereditary Diffuse Gastric Cancer to improve equitable access, early detection and surveillance for high-risk individuals. All participants will have screening as per conventional syndrome-specific surveillance recommendations. Half the participants (experimental cohort) will also have cfDNA analysis at least three times a year, with abnormal results triggering dedicated clinical imaging and diagnostic evaluation, and heightened surveillance. Vetted by our patient advisors, validated patient-reported outcome and experience measures assessing participant psychosocial outcomes, engagement, and test preferences will be administered to both arms. Our goal is to inform if and how cfDNA analysis could be implemented into routine clinical care and offer a path to equitable and more convenient cancer screening for all high-risk Canadians.
    DOI:  https://doi.org/10.1038/s41431-026-02014-z
  5. NPJ Precis Oncol. 2026 Jan 24.
    Ultrasensitive ctDNA monitoring reveals early predictors of immunotherapy response in advanced cancer.
    Daisuke Nishizaki, Allison Law, Bailiang Li, Charles Abbott, Yi Chen, Suzanna Lee, Rachel Pyke, Kathleen Keough, Gregory A Daniels, Kay T Yeung, Sean M Boyle, Richard O Chen, Shumei Kato.
      Circulating tumor DNA (ctDNA)-based response assessment is appealing but limited by conventional analytical thresholds. We utilized a whole genome sequencing based, tumor-informed ultrasensitive ctDNA assay which tracked ~1800 somatic mutations to analyze 227 longitudinal plasma samples from 39 patients with advanced/metastatic cancers receiving immune checkpoint inhibitors (ICIs). ctDNA was detected from 2.0-239,315 PPM (median limit of detection: 1.77 PPM), with 33% of positive detections below 100 PPM. Early molecular response, defined as >50% ctDNA reduction or sustained ctDNA negativity from baseline to first follow-up, strongly predicted improved progression-free survival (PFS) (hazard ratio (HR) = 0.09, 95% CI: 0.02-0.39, p = 0.001) and was independently prognostic of PFS. Molecular complete response (mCR), defined as any ctDNA clearance, predicted overall survival and PFS, with 1-year PFS of 87% in mCR patients versus 16% in non-mCR patients (HR = 0.14, 95% CI: 0.04-0.50, p = 0.003). The high-sensitivity ctDNA monitoring may enable precise, real-time evaluation of ICI response to guide clinical decision-making.
    DOI:  https://doi.org/10.1038/s41698-026-01287-3
  6. J Cell Mol Med. 2026 Feb;30(3): e71019
    Emerging Role of ctDNA Fragmentomics and Epigenetic Signatures in the Early Detection, Minimal Residual Disease Assessment, and Precision Monitoring of Renal Cell Carcinoma.
    Hossam Kamli, Najeeb Ullah Khan.
      Renal cell carcinoma (RCC) presents a significant global health challenge, with a substantial proportion of patients diagnosed with advanced or metastatic disease due to the limitations of current diagnostic imaging and the lack of validated non-invasive biomarkers. These conventional methods, including computed tomography and magnetic resonance imaging, often lack the sensitivity and specificity to differentiate benign from malignant small renal masses reliably or to detect minimal residual disease (MRD) post-treatment. This review explores the transformative potential of liquid biopsy, explicitly focusing on circulating tumour DNA (ctDNA) fragmentomics and epigenetic signatures, to overcome these clinical hurdles. This review also explores how the analysis of ctDNA fragmentation patterns-such as size distribution, end motifs, and nucleosome footprints-provides a mutation-independent method to enhance RCC detection, even in low-shedding tumours. Concurrently, RCC-specific epigenetic alterations, particularly DNA methylation profiles, offer particular biomarkers for early detection, tumour classification, and prognostication. This Review examines evidence that integrating these multi-analyte approaches-combining fragmentomic and epigenetic data-synergistically improves diagnostic accuracy, enables sensitive MRD assessment, and allows precision monitoring of treatment response and tumour evolution. Despite existing technical and biological challenges, the convergence of ctDNA fragmentomics and epigenetic profiling heralds a new era for the non-invasive, dynamic, and personalised management of RCC, promising to improve patient outcomes through earlier intervention and tailored therapeutic strategies.
    Keywords:  ctDNA; early detection; epigenetic signatures; fragmentomics; minimal residual disease; precision monitoring; renal cell carcinoma
    DOI:  https://doi.org/10.1111/jcmm.71019
This page is being maintained by Thomas Krichel. It was last updated on 2026‒02‒15 at 21:52.