bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–04–26
nine papers selected by
Lara Paracchini, Humanitas Research
  1. Spatial integration of protein and chromosomal states reveals early copy number changes and genotype-associated immune neighborhoods in serous ovarian cancer evolution.
  2. plasmaCHORD: A Machine Learning Approach to Distinguish Clonal Hematopoiesis-Derived Variants in Liquid Biopsies from Patients with Solid Tumors.
  3. Correction: Hereditary gynecological cancer management in women with Lynch syndrome: a survey across Europe.
  4. Ciliated Cells Drive Critical STING-Mediated Tumor Suppression in the Fallopian Tube Epithelium.
  5. Integrated single-cell whole genome sequencing and spatial transcriptomics reveal intra-tumoral heterogeneity in ovarian cancer.
  6. Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers.
  7. Beyond mutations: epigenetic and fragmentomic landscapes of cfDNA in lung cancer.
  8. A high-resolution spatial map of cilia-associated proteins in the human fallopian tube.
  9. Prevention and inequalities will determine success of England's cancer plan.
  1. Cancer Discov. 2026 Apr 18.
    Spatial integration of protein and chromosomal states reveals early copy number changes and genotype-associated immune neighborhoods in serous ovarian cancer evolution.
    Tanjina Kader, Yu-An Chen, Clemens B Hug, Jia-Ren Lin, Jeremy L Muhlich, Shannon Coy, Euihye Jung, Lauren E Schwartz, Thomas Fazio, Crystal Chiu, Scott T Ryall, Charles W Drescher, Peter K Sorger, Ronny Drapkin, Sandro Santagata.
      Detecting chromosomal copy-number alterations together with protein-defined cell states in intact tissue is critical for understanding early clonal evolution and microenvironmental interactions in cancer. We developed ORION-FISH, which integrates high-plex tissue imaging with a morphology-preserving DNA-FISH workflow and single-cell registration, yielding measurements concordant with clinical FISH. In High Grade Serous Ovarian Carcinoma (HGSOC), ORION-FISH recapitulated known chromosomal changes while revealing subclonal heterogeneity missed by targeted sequencing. Applied to serous tubal intraepithelial carcinomas (STICs), precursors of HGSOC, ORION-FISH identified intermixed epithelial cells with MYC or CCNE1 copy-number gains, as well as concurrent alterations associated with distinct immune microenvironments. In addition, epithelial cells with MYC and CCNE1 copy-number gains were detected in morphologically normal fallopian tube epithelium, along with rare MDM4 increases across epithelial lineages. Together, ORION-FISH provides a framework linking chromosomal copy number states to protein-defined phenotypes within preserved tissue architecture, enabling context-aware interrogation of early copy-number diversification at single-cell resolution.
    DOI:  https://doi.org/10.1158/2159-8290.CD-26-0171
  2. Clin Cancer Res. 2026 Apr 19. OF1-OF16
    plasmaCHORD: A Machine Learning Approach to Distinguish Clonal Hematopoiesis-Derived Variants in Liquid Biopsies from Patients with Solid Tumors.
    MEDOCC Group
       PURPOSE: Targeted next-generation sequencing (NGS) of cell-free DNA (cfDNA) enables comprehensive molecular profiling and can guide the selection of genotype-targeted therapies. However, the detection of variants derived from clonal hematopoiesis (CH) is a significant confounder in liquid biopsies.
    EXPERIMENTAL DESIGN: Using a training cohort of 426 variants identified in cfDNA NGS from 225 patients with stage I to IV solid tumors, we developed plasma Clonal Hematopoiesis ORigin Detection (plasmaCHORD), a machine learning model that includes fragment-, variant-, and patient-level features to distinguish between tumor and CH origin for each variant detected by liquid biopsies. Model performance was assessed by comparison with the reference origin for each plasma variant determined from matched white blood cell and tumor NGS. Following the locking of the model parameters, we applied plasmaCHORD to an independent validation cohort of 1,418 plasma variants detected in 114 patients with metastatic cancers, as well as to cfDNA NGS from patients enrolled in a prospective clinical trial (NCT05585684).
    RESULTS: plasmaCHORD predicted tumor origin versus CH origin in the training set with high accuracy (AUC = 0.94). In the independent validation cohort, the locked model maintained similar overall accuracy (AUC = 0.9) and demonstrated significant improvement in accuracy for clinically significant genes. When applied to clinically challenging cases in the context of a precision oncology clinical trial, plasmaCHORD precisely determined variant origin, preventing mismatches with genotype-targeted therapies.
    CONCLUSIONS: plasmaCHORD, a multifeature machine learning model, can significantly enhance the ability to identify bona fide tumor variants in routine plasma-only NGS, addressing a critical need for implementing liquid biopsy-guided therapy by minimizing misinterpretation caused by CH.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-25-0976
  3. Fam Cancer. 2026 Apr 22. pii: 44. [Epub ahead of print]25(2):
    Correction: Hereditary gynecological cancer management in women with Lynch syndrome: a survey across Europe.
    ERN GENTURIS Survey Group
      
    DOI:  https://doi.org/10.1007/s10689-026-00553-4
  4. Cancer Res. 2026 Apr 22. OF1-OF18
    Ciliated Cells Drive Critical STING-Mediated Tumor Suppression in the Fallopian Tube Epithelium.
    Jose A Colina, Maria Sol Recouvreux, Alexander M Sobeck, Benjamin K Johnson, Yinzhi Lin, Sreeja C Sekhar, Rita A Avelar, Gabriela Rivera-Gonzalez, Yali Zhai, Harini Ram, Amber Fatima, Paula DiBenedetto, Justin Baldassarre, Grace McIntyre, Jessica Teitel, Michele L Dziubinski, Noah Puleo, Jane Miglo, Karan Bedi, Hui Shen, Dafydd Thomas, Jutta Huvila, Dawn R Cochrane, Ronny Drapkin, Yu L Lei, Joanna E Burdette, Stephanie L Skala, David G Huntsman, Kathleen R Cho, Sandra Orsulic, Analisa DiFeo.
      Mitigating DNA damage in the fallopian tube epithelium (FTE) is essential for preventing tubo-ovarian high-grade serous carcinoma (HGSC). In this study, we demonstrated that the stimulator of interferon genes (STING) is abundantly expressed in the ciliated cells of the FTE and functions as a critical immune-independent tumor suppressor. In patient samples, mouse models, and organoid systems, ciliated cells mounted a dual protective response to ovulation-associated genotoxic stress: intrinsic STING-driven apoptosis and extrinsic clearance of neighboring damaged secretory cells via TNFα secretion. This surveillance mechanism markedly limited DNA damage accumulation within the epithelial microenvironment. Crucially, although these mechanisms were vital for maintaining homeostasis and reducing genomic instability, they failed to affect p53-deficient precursor lesions as both the intrinsic and extrinsic proapoptotic processes relied on functional p53 signaling. These findings redefine ciliated cells as key gatekeepers of genome integrity rather than passive bystanders and implicate the early loss of STING-high ciliated cells as a pivotal event in HGSC initiation.
    SIGNIFICANCE: STING-high ciliated fallopian tube cells function as immune-independent active guardians of genomic integrity whose loss creates a permissive niche for high-grade serous carcinoma initiation, which could inform prevention and treatment strategies.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-25-1527
  5. Cancer Res Commun. 2026 Apr 20.
    Integrated single-cell whole genome sequencing and spatial transcriptomics reveal intra-tumoral heterogeneity in ovarian cancer.
    Rania Bassiouni, Yuxin Jin, Lee D Gibbs, Jing Qian, Solomon O Rotimi, Heather Miller, Michelle G Webb, Seeta Rajpara, Javier Arias-Stella, David W Craig, Lynda Roman, John D Carpten.
      The mortality rate of ovarian cancer remains disproportionately high compared to its incidence. This is partly due to a high level of intra-tumoral heterogeneity, driven by genomic instability, that promotes disease recurrence and treatment failure. In this study, we describe degrees of heterogeneity revealed by single-cell whole genome sequencing and spatial transcriptomics of five late-stage, treatment-naïve primary epithelial ovarian carcinomas, including high grade serous and clear cell subtypes. All samples exhibited widespread copy number aberrations, with greatest intra-specimen diversification in regions of copy number gain. Diversification was also associated with whole genome doubling in all samples. In two samples, we identify persistent, clonal pseudo-diploid cells evolutionarily consistent with a pre-malignant phenotype. In multi-clonal samples, we interpret clonal evolution in the context of single cell copy number, loss of heterozygosity analysis, and somatic mutations, and correlate these with tissue histology and gene expression programs. In one high grade serious carcinoma, we identify functionally consequential copy number alterations that contribute to molecular diversity, cell proliferation, and inflammation in a minor clone that persisted without major expansion alongside a more complex major clone. In another clear cell carcinoma, we describe a complex evolutionary history including a spontaneous functional reversion of a CTNNB1 driver mutation in a secondary clone, which correlated with a switch in oncogenic expression programs. These examples highlight various consequences of genomic instability on clonal heterogeneity and plasticity in ovarian cancer.
    DOI:  https://doi.org/10.1158/2767-9764.CRC-25-0795
  6. J Ovarian Res. 2026 Apr 23.
    Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers.
    Akemi Morimoto, Takashi Matsumoto, Norifumi Teramoto, Sakiko Murakami, Tomoka Usami, Junko Murai, Takashi Sugiyama.
      
    Keywords:  Genomic instability score (GIS); Homologous recombination deficiency (HRD); Interval debulking surgery; Neoadjuvant chemotherapy; Ovarian cancer
    DOI:  https://doi.org/10.1186/s13048-026-02101-1
  7. Expert Rev Mol Diagn. 2026 Apr 23.
    Beyond mutations: epigenetic and fragmentomic landscapes of cfDNA in lung cancer.
    Jing Liu, Laura S E Schulz, Qing Zhou.
       INTRODUCTION: Lung cancer is the most frequently diagnosed cancer worldwide and the leading cause of cancer-related mortality. Cell-free DNA (cfDNA) has emerged as a powerful biomarker in cancer detection. Early diagnostics efforts often leverage cancer-associated mutations present in cfDNA, but beyond such mutation-based assays, recent advances have shed light on other non-mutational features. The analysis of cfDNA epigenetic profiles and fragmentation patterns, known as 'fragmentomics,' has revealed a wealth of data to explore in noninvasive lung cancer diagnosis.
    AREAS COVERED: This review will explore this new narrative, summarizing the current understanding and use of cfDNA epigenetic modifications and fragmentomic patterns, while integrating findings to illustrate their vast potential in early-stage detection and therapeutics. By considering a range of epigenetic and fragmentomic features, cfDNA methylation (5mC, 5hmC), histone modifications, size profiles, and end signatures, this review highlights how the multidimensional integration of such signals shows promise in refining early-stage lung cancer and guiding therapeutic decisions.
    EXPERT OPINION: cfDNA epigenetic and fragmentomic analyses represent a transformative frontier in lung cancer diagnostics and monitoring. While these approaches demonstrate significant potential, most studies are limited by modest cohort sizes and reports of survival benefits, underscoring the need for large-scale validation and deeper mechanistic understanding.
    Keywords:  Fragmentomics; Liquid biopsy; early cancer detection; epigenetics; lung cancer
    DOI:  https://doi.org/10.1080/14737159.2026.2665256
  8. Nat Commun. 2026 Apr 20. pii: 3616. [Epub ahead of print]17(1):
    A high-resolution spatial map of cilia-associated proteins in the human fallopian tube.
    Feria Hikmet, Andreas Digre, Jan Niklas Hansen, Samantha B Schon, Emma Lundberg, Matts Olovsson, Mathias Uhlén, Loren Méar, Cecilia Lindskog.
      Molecular alterations in the fallopian tubes play a pivotal role in the development of cancer and reproductive disorders, yet their molecular landscape at the protein level remains poorly defined. Here, we map key fallopian tube proteins at single-cell resolution utilizing an integrated transcriptomics and proteomics approach. Based on RNA-seq analysis, we identify 310 genes with elevated expression in the fallopian tube, the majority of which are associated with motile cilia function. We spatially characterize 133 of the corresponding proteins in the fallopian tube and other human tissues with motile cilia to subcellular structures of ciliated cells, validating the findings with single-cell RNA-seq and mass-spectrometry data. Eleven proteins previously only studied on the transcript level without information in cilia databases are further analyzed in a hydrosalpinx patient, showing a thinner epithelium, lower density of FOXJ1 expression, and reduced expression of FHAD1, RIIAD1, and C2orf81. Our high-resolution spatial map aids in dissecting the pathways underlying infertility and diseases linked to cilia-specific functions.
    DOI:  https://doi.org/10.1038/s41467-026-71692-6
  9. BMJ. 2026 Apr 24. 393 s704
    Prevention and inequalities will determine success of England's cancer plan.
    Padmanabhan Badrinath.
      
    DOI:  https://doi.org/10.1136/bmj.s704
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