bims-ovdlit 2026-05-31 papers

Issue of 2026–05–31
nine papers selected by
Lara Paracchini, Humanitas Research

Mod Pathol. 2026 May 25. pii: S0893-3952(26)00062-1. [Epub ahead of print] 101019

Gynecologic Tumors and Precursor Lesions, Including p53-Aberrant Atypical Hyperplasia-like Endometrial Lesions, in Li-Fraumeni Syndrome.

Yurika Nishikawa, Ozge Ceyhan-Birsoy, Pier Selenica, Diana Mandelkar, M Herman Chui.

Li-Fraumeni syndrome (LFS), caused by germline TP53 (g-TP53) mutation, predisposes to a wide range of early-onset malignancies, but gynecologic tumors are relatively uncommon. We sought to define the spectrum of neoplasms and atypical lesions of the female reproductive tract in LFS patients. Histomorphologic review was performed on tumors and gynecologic tissues from biopsy or resection specimens from 20 female patients with g-TP53 mutations. Gynecologic cancers (n=7) were comprised of high-grade serous carcinomas of tubo-ovarian/primary peritoneal origin (n=3), high-grade endometrioid ovarian carcinoma (n=1), endometrial serous carcinoma (n=1), and leiomyosarcomas (uterine, n=1, ovarian, n=1). Morphological features were indistinguishable from sporadic cases. With exception of one case, somatic inactivation of the remaining TP53 allele was identified, by loss-of-heterozygosity or deep deletion. Other abnormal lesions, which exhibited aberrant p53 expression by immunohistochemistry, included serous tubal intraepithelial carcinoma (STIC, n=2), uterine smooth muscle tumor of uncertain malignant potential (STUMP, n=1), and endometrial glandular lesions, morphologically resembling atypical hyperplasia (n=4, median age: 33). Immunohistochemistry on p53-aberrant atypical hyperplasia-like lesions revealed PAX2 loss (3/4), nuclear beta-catenin (1/3), and decreased PTEN (2/3); molecular analysis on 2 cases revealed TP53 loss-of-heterozygosity, with concomitant KRAS or PTEN mutation. These lesions resolved with progestin therapy (n=2) or did not recur following hysterectomy (n=2). In morphologically benign tissues, p53 immunohistochemistry revealed variable staining patterns, including wildtype only, discrete foci of aberrant expression, and diffuse p53 overexpression in nearly all cells (associated with the g-TP53 p.Arg337His founder variant). Our findings demonstrate that g-TP53 mutations can drive the pathogenesis of gynecologic tumors that are usually defined by somatic TP53 mutations. A novel p53-aberrant endometrial glandular lesion, occurring in young patients with LFS, likely represents an unusual form of endometrial atypical hyperplasia, rather than serous carcinoma. In morphologically benign tissues, aberrant p53 expression in numerous discrete foci or diffusely across nearly all cells should prompt consideration of an underlying g-TP53 mutation.

Keywords: Li-Fraumeni syndrome; TP53; atypical hyperplasia; endometrioid carcinoma; high-grade serous carcinoma; precursor lesion

DOI: https://doi.org/10.1016/j.modpat.2026.101019

medRxiv. 2026 May 14. pii: 2026.05.11.26352922. [Epub ahead of print]

Liquid Biopsy of HPV Cell-Free DNA Enables Blood-Based Early Detection and Molecular Stratification of HPV-Associated Cancer and Precancer Stages.

Qin Wang, Samuli Eldfors, Sangmi Sandra Lee, Dipon Das, Yana Al-Inaya, Gjystina Lumaj, Eliana T Epstein, Shriya Shukla, Emma Ricart, Harsharan Dhillon, Juniper Lake, Shun Hirayama, Viktor A Adalsteinsson, Michael G Drage, Doga C Gulhan, Benjamin T Davis, Daniel L Faden.

Liquid biopsies targeting circulating tumor DNA enable noninvasive cancer detection but lack sensitivity in pre- and early-cancer stages, where clinical benefits would be greatest. Human papillomavirus (HPV) causes six cancer types, accounting for 5% of all cancers worldwide. Targeting HPV cell-free (cf)DNA offers a compelling opportunity to overcome current liquid biopsy constraints due to its unique tumor-specific origin, lack of sequence homology to the human genome, and the high viral-to-human copy ratio per cell. Utilizing HPV-associated anal cancer and precancer as a model, here we applied a custom, multi-feature HPV whole-genome liquid biopsy to biobanked and prospective screening cohorts spanning the HPV infection-precancer-cancer continuum. HPV cfDNA was detected years before cancer diagnosis and as early as the infection stage, with increasing detection as stages advanced. Genomic hallmarks of HPV malignancy, including HPV integration, PIK3CA mutations, and 3q amplification, were detected exclusively in cancer, while precancers exhibited distinct HPV genotypes. Fragmentomics analysis of HPV cfDNA revealed stage-informative signatures reflecting viral epigenetic changes during carcinogenesis. A unified classifier incorporating genomic and fragmentomics features achieved a mean AUC of 0.77 for identifying cancer and high-grade precancer, stages requiring clinical intervention. Together, these findings demonstrate the feasibility of blood-based screening and molecular risk stratification for HPV-associated cancer and precancer.
Teaser: Profiling blood HPV cell-free DNA detects cancer years early and distinguishes precancers needing intervention from surveillance.

DOI: https://doi.org/10.64898/2026.05.11.26352922

NPJ Precis Oncol. 2026 May 25.

Circulating cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) in oncology: from technological advances to clinical applications.

Edoardo Francini, Sara Bleve, Giuseppe Nicolo Fanelli, Mara Serena Serafini, Filippo Pederzoli, Alessandra Ferri, Erika Minonne, Jacopo Venturini, Silvia Rodrigues, Hubert Pakula, Cristian Lolli, Massimo Cristofanilli, Pier Vitale Nuzzo.

Circulating cell-free DNA (cfDNA) methylation profiling enables minimally invasive cancer detection and monitoring. Among available methods, cfMeDIP-seq is a sensitive, scalable, bisulfite-free approach suitable for low-input cfDNA. This review summarizes its principles, comparative technologies, and clinical applications, including early detection, tumor classification, and minimal residual disease monitoring. Despite promising performance, challenges remain in standardization and validation, while emerging multi-omic integrations may further enhance its role in precision oncology.

DOI: https://doi.org/10.1038/s41698-026-01507-w

Crit Rev Oncol Hematol. 2026 May 26. pii: S1040-8428(26)00276-3. [Epub ahead of print]224 105389

Emerging biomarkers for the early detection of high-grade serous tubo-ovarian cancer.

Sara Atiq, Nikola A Bowden, Kristina Warton, Michelle W Wong-Brown.

High-grade serous tubo-ovarian cancer remains one of the deadliest gynaecological malignancies, mostly due to vague symptoms and late-stage diagnosis. This review explores the strengths and limitations of current early detection biomarkers, specifically for high-grade serous tubo-ovarian cancer. While significant progress has been made, challenges remain with low sensitivity and specificity of detection biomarkers and the need for multimodal approaches and validation in diverse populations. This review explores biomarkers with demonstrated potential for detecting early-stage high-grade serous tubo-ovarian cancer through non-invasive methods in the general population and have the potential to improve patient outcomes. To date, there is no biomarker-based screening or early diagnosis test that has been shown to reduce ovarian cancer mortality in the larger population. This review focuses on current and emerging biomarkers in high-grade serous tubo-ovarian cancer, including genomic and proteomic changes that have diagnostic potential. While there are no biomarkers that have been approved for population-wide screening, evidence strongly supports DNA methylation-based liquid biopsy approaches for screening and early detection of high-grade serous tubo-ovarian cancer. This review highlights emerging biomarkers for early detection through minimally invasive methods and underscores the challenges of existing detection biomarkers.

Keywords: Biomarkers; DNA methylation; Early detection; Liquid biopsy; Ovarian cancer

DOI: https://doi.org/10.1016/j.critrevonc.2026.105389

Nat Rev Genet. 2026 May 29.

Advancing the applications of liquid biopsies in oncology.

Sara Valpione, Alexandra Clipson, Dominic G Rothwell, Caroline Dive, Florent Mouliere.

Liquid biopsies are increasingly important tools for precision oncology. Although their ability to detect the minute amounts of cancer biomarkers present in biofluids is improving, limitations remain regarding accurate detection of certain pathologies, analytical validation, application range and broad clinical utility. Emerging methods harness multi-omic data from a range of circulating analytes that can be released from various sources via distinct biological processes, thereby providing complementary and more sensitive information. Modulating the cellular release of these analytes and their half-lives in blood can be exploited to inform on cancer detection, treatment selection, response and/or toxicity. Simultaneously, efforts to miniaturize liquid biopsies to capitalize on their minimally invasive nature will accelerate turnaround time and enable continuous and ideally remote monitoring of circulating analytes. Together, these advances towards next-generation liquid biopsies will substantially improve patient experience.

DOI: https://doi.org/10.1038/s41576-026-00974-y

Curr Oncol Rep. 2026 May 23. pii: 59. [Epub ahead of print]28(1):

Liquid Biopsy in Modern Oncology: Advances, Challenges, and Future Perspectives in Early Cancer Detection, Minimal Residual Disease, and Dynamic Patient Monitoring.

Yareli Lizbeth Rojas-Salazar, Emiliano Gómez-Montañez, Jorge Gustavo Rojas-Salazar.

PURPOSE OF REVIEW: Liquid biopsy has emerged as a minimally invasive approach to overcome the limitations of tissue biopsy in oncology. This review aims to synthesize recent advances in its clinical applications, particularly in early cancer detection, therapeutic monitoring, and minimal residual disease (MRD), while discussing current challenges, regulatory perspectives, and future directions.
RECENT FINDINGS: Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles, and epigenetic markers are the most extensively studied biomarkers, in which clinical trials such as TRACERx and DYNAMIC have demonstrated that ctDNA monitoring enables earlier detection of recurrence and guides adjuvant therapy decisions more precisely than standard imaging. Commercially validated assays, including Guardant360 CDx, FoundationOne Liquid CDx, and Epi proColon, have received regulatory approval, reflecting growing clinical adoption; however, limitations persist, including reduced sensitivity in low-tumor burden settings, technical variability between platforms, and the risk of false positives from clonal hematopoiesis. Ongoing research highlights the promise of multi-omic approaches and the integration of artificial intelligence to improve sensitivity, capture tumor heterogeneity, and provide predictive insights into treatment response and resistance. Liquid biopsy represents a paradigm shift in precision oncology by enabling real-time, longitudinal tumor profiling. Although significant barriers remain, such as cost, accessibility, and lack of standardization, technological innovations and large-scale validation studies are paving the way for its routine clinical integration.

DOI: https://doi.org/10.1007/s11912-026-01799-y

Gynecol Pelvic Med. 2024 ;7 30

Is it time to add BRCA1 promoter methylation testing in the arsenal of ovarian cancer diagnostic tools?

Monica D Levine, Leigha Senter, David M O'Malley.

Keywords: BRCA1 promoter methylation; Ovarian cancer; homologous recombination deficiency (HRD)

DOI: https://doi.org/10.21037/gpm-23-54