bims-ovdlit 2026-07-19 papers

Issue of 2026–07–19
seven papers selected by
Lara Paracchini, Humanitas Research

Gynecol Oncol Rep. 2026 Aug;66 102157

Lights genes action: Video strategy for BRCA1/2 patient education.

Tina Karimaghaie, Genevieve Fasano, Steve Lopez, Samantha Min, Laura Keenahan, Muhammad Danyal Ahsan, Sue Friedman, Emily S Epstein, Ravi N Sharaf, Lisa Newman, Melissa K Frey.

Objectives: Pathogenic variants (PVs) in the BRCA1 and BRCA2 ( BRCA1/2) genes increase lifetime risk of several cancers including breast and ovarian. Communicating complex genetic risk and management strategies can be challenging. Digital education tools, like short videos, can provide standardized, accessible information to support patient understanding and family communication.
Methods: A short educational video reviewing BRCA1/2-associated cancer risks, guideline-based screening, and risk-reduction strategies was developed using National Comprehensive Cancer Network (NCCN) recommendations in patient-centered language. From July-August 2024, patients with known BRCA1/2 PVs attending a gynecologic oncology clinic were offered video access via a QR code and invited to complete a voluntary survey assessing usability, satisfaction, perceived usefulness, trustworthiness, and potential value for family communication. Survey responses were summarized descriptively.
Results: Of 34 patients offered the video, 32 (94%) viewed it, of which 28 (88%) completed the survey. Median age of participants was 43 years (interquartile range, [IQR]: 35-60 years). All participants were female, 68% White, 11% Hispanic or Latino, 46% BRCA1 PVs, and 54% BRCA2 PVs. Most participants rated the video as very easy to use (96%), very understandable (96%), and satisfying (86%), with 79% finding the content useful and 64% finding the video helpful for communicating risk with relatives. Qualitative feedback highlighted clarity and usefulness for newly diagnosed individuals.
Conclusions: These findings suggest that a brief educational video on BRCA1/2 risk was feasible, highly acceptable, and perceived as useful by participants. Video-based education may serve as an effective adjunct to clinical counseling and facilitate communication of hereditary cancer risk with relatives.

DOI: https://doi.org/10.1016/j.gore.2026.102157

Expert Rev Mol Diagn. 2026 Jul 16.

Protein signatures for the early detection of endometrial cancer in cervico-vaginal fluid.

Kelechi Njoku, Molly Dore, Jean-Ellen Johnson, Jennifer C Davies, Andrew Pierce, Davide Chiasserini, Ananya Choudhury, Anthony D Whetton, Richard Unwin, Emma J Davidson.

INTRODUCTION: Endometrial cancer is the most common gynecological malignancy in high-income countries. Although postmenopausal bleeding is its cardinal presenting symptom, only 5-10% of women with postmenopausal bleeding have malignancy. There is therefore a need for accurate, minimally invasive diagnostic tests. Proteins detectable in proximal biofluids, particularly cervicovaginal fluid (CVF), represent promising biomarkers because they reflect the functional biology of the tumor and can be measured using clinically translatable immunoassays.
AREAS COVERED: This review critically evaluates the evidence for CVF protein biomarkers in the early detection of endometrial cancer. Three protein signatures show the greatest promise: a five-protein panel (HPT, LGALS3BP, FGA, LY6D, IGHM; AUC 0.95), a 12-protein inflammatory panel (AUC 0.91), and an 11-protein multivariate panel (AUC 0.92), all approaching or meeting thresholds for clinical consideration. We also discuss the biological relevance of these proteins and highlight the methodological, analytical and translational challenges that must be addressed before clinical implementation.
EXPERT OPINION: CVF provides a unique, minimally invasive sampling medium owing to the anatomical continuity between the uterine cavity and lower genital tract. While current evidence is encouraging, most candidate biomarkers remain exploratory and require rigorous validation in large, prospective multicentre studies before incorporation into routine clinical practice.

Keywords: Endometrial cancer; cervico-vaginal fluid; diagnostic biomarkers; early-detection; liquid biopsy; proteins

DOI: https://doi.org/10.1080/14737159.2026.2705465

Int J Mol Sci. 2026 Jun 25. pii: 5739. [Epub ahead of print]27(13):

Low-Pass Nanopore Sequencing of Plasma cfDNA Reveals Fragmentomic, Epigenomic, and Age-Associated Signatures Under Ultra-Low-Coverage Conditions.

Andrey Eremin, Alexander Sergeev, Tsimur Hasanau, Maria Zvereva.

Circulating cell-free DNA (cfDNA) enables minimally invasive assessment of chromatin organization and DNA modifications. Whether such information can be reliably recovered under conditions of limited plasma input (below 1 mL) and ultra-low sequencing depth remains unclear. We performed low-pass whole-genome Oxford Nanopore sequencing (down to 0.01× coverage) of plasma cfDNA from young and elderly donors and jointly analyzed fragment length distributions and base modifications (5mC, 5hmC, 6mA). In parallel, we analyzed an enzymatically fragmented model DNA system to assess whether controlled in vitro fragmentation can reproduce cfDNA-like nucleosomal profiles and associated modification patterns. Despite shallow coverage, cfDNA samples displayed reproducible mono-, di-, tri-, and tetra-nucleosomal peaks, indicating that major fragmentomic features can be retained under ultra-low-coverage conditions. Modification-aware basecalling enabled exploratory quantification of global modification fractions across nucleosomal size classes and nomination of candidate group-specific modification loci. Overall, these results support the feasibility of low-pass nanopore sequencing as an exploratory framework for simultaneous cfDNA fragmentomic and epigenomic profiling in low-input studies.

Keywords: aging; cfDNA; epigenomics; fragmentomics; low-pass; nanopore sequencing

DOI: https://doi.org/10.3390/ijms27135739

Trends Cancer. 2026 Jul 15. pii: S2405-8033(26)00140-8. [Epub ahead of print]

Under pressure: clonal hematopoiesis in patients receiving cancer therapy.

Vincent Rondeau, Elina K Cook, Robert J Vanner.

In clonal hematopoiesis (CH), hematopoietic stem cells (HSCs) with mutations conferring a fitness advantage preferentially expand under evolutionary constraints. Over the last decade, cancer therapy has emerged as a selective pressure contributing to high rates of CH in patients with hematological and nonhematological cancers. Distinct chemotherapies, radiotherapies, immunotherapies, and targeted cancer therapies shape somatic evolution by inducing de novo mutations and by conferring a selective advantage to pre-existing CH clones. Such expansion may influence treatment response and toxicity, and is linked to the development of therapy-related myeloid neoplasms. CH prevalence will continue to increase as treatment options expand, cancers are detected earlier, and patients live longer. Managing CH and its adverse effects has the potential to improve cancer outcomes and survivorship.

Keywords: chemotherapy; clonal evolution; clonal hematopoiesis; hematopoietic stem cell; immunotherapy; radiation

DOI: https://doi.org/10.1016/j.trecan.2026.06.012

Genome Res. 2026 Jul 14. pii: gr.281428.125. [Epub ahead of print]

The impact of sex, age, and genetic ancestry on DNA methylation across tissues.

Winona Oliveros, Jose Miguel Ramirez, Maria Sopena-Rios, Pau Clavell-Revelles, Marta Mele.

Understanding the consequences of individual DNA methylation variation is crucial for advancing our knowledge of human biology and disease. Yet, the collective impact of individual traits on DNA methylation and their downstream effects on gene expression across human tissues remain poorly understood. Here, we quantify the contributions of sex, age, genetic ancestry, and BMI on autosomal DNA methylation variation across 9 human tissues and 424 individuals from the Genotype-Tissue Expression project. We show that genetic ancestry and age have a greater impact on DNA methylation than sex, with aging effects being more widespread but less pronounced. On average, less than 10% of the gene expression variation in sex, age, and ancestry are mediated by DNA methylation differences, with ancestry showing the largest proportion of mediation. We further show that ancestry-associated DNA methylation differences accumulate at CpG sites with extreme methylation states and are largely under genetic control. The female autosomal genome exhibits consistent hypermethylation across tissues at Polycomb-repressed regions. Ultimately, we show that age-related Polycomb target hypermethylation is observed across multiple tissues, but not in the gonads. Our multi-individual, multi-tissue approach defines the key drivers of human DNA methylation variation in healthy conditions, establishing a baseline for the interpretation of DNA methylation changes in disease contexts.

DOI: https://doi.org/10.1101/gr.281428.125