bims-ovdlit 2026-06-14 papers

Issue of 2026–06–14
seven papers selected by
Lara Paracchini, Humanitas Research

J Gynecol Oncol. 2026 May 27.

Tubal epithelial alterations: evolving concepts.

The fallopian tube has emerged as a central organ in the pathogenesis of ovarian cancer, particularly high-grade serous carcinoma (HGSC). Detailed histopathological and molecular analyses have revealed a diverse spectrum of tubal epithelial alterations with varying malignant potentials. This review outlines key lesions including secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial lesion (STIL), serous tubal intraepithelial carcinoma (STIC), β-catenin signatures, endometrioid tubal intraepithelial neoplasia, and papillary tubal hyperplasia (PTH). The p53 signature, STIL, and STIC are changes originating from secretory cells with underlying TP53 alterations. However, recent findings suggest that these lesions do not necessarily represent a continuous sequence in terms of risk of progression to HGSC. Advances in molecular biology have enabled the estimation of malignant potential of individual lesions. SCOUTs, particularly Type II are thought to be precursors of endometrioid carcinoma. While SCOUTs are frequently observed in the general population, endometrioid carcinoma of the fallopian tube remains extremely rare. PTH has traditionally been regarded as a reactive phenomenon; however morphological and molecular overlaps with low-grade serous carcinoma have recently been suggested. These findings underscore the complexity and heterogeneity of tubal epithelial alterations and suggest that not all lesions follow a linear tumorigenic sequence. Continued integration of morphological, molecular, and spatial analyses will be essential for refining our understanding of tubal pathology and its contribution to gynecological carcinogenesis.

Keywords: Beta Catenin; Tumor Suppressor Protein p53; sFallopian Tubes

DOI: https://doi.org/10.3802/jgo.2026.37.e121

Cell Rep Med. 2026 Jun 12. pii: S2666-3791(26)00283-1. [Epub ahead of print] 102866

Toward generalizable prediction of cancer signal using a cell-free DNA language model.

Yang Xu, Hua Bao, Daxin Huang, Kun Zhang, Junfei Zhu, Liu Yang, Shengling Fu, Zhili Chang, Jinfeng Zhang, Shuang Chang, Baihan Zhu, Shuyu Wu, Shanshan Yang, Xue Wu, Yang Shao.

Cell-free DNA can be used for early cancer detection, minimal residual disease monitoring, and post-treatment risk stratification. However, current assays are often designed for a single purpose and rely on deep or broad sequencing panels that capture only a small fraction of tumor-derived signals, limiting transferability, increasing cost, and reducing scalability. Fragmentia-AI is an artificial intelligence language model that learns fragment-level sequence patterns in tumor-derived cell-free DNA. Instead of focusing on mutations, it uses the structure of cell-free DNA to detect cancer signals in a partially panel-agnostic manner from ultra-low sequencing input, approximately 0.1%-1% of conventional depth. The model performs well across cancer types and clinical settings, including monitoring after surgery or immunotherapy, and in samples with low variant allele frequencies or no detected mutations. Fragment-level analyses identify shorter fragments and tumor-derived sequence patterns across panels of different sizes and ultra-low-pass whole-genome sequencing in multiple cohorts.

Keywords: artificial intellegence; cell free DNA; early cancer detection; fragmentomics; large language model; minimal residual disease; ultra-low sequencing; whole genome sequencing

DOI: https://doi.org/10.1016/j.xcrm.2026.102866

Front Oncol. 2026 ;16 1879673

Editorial: Early detection, cancer interception, et al.: translating the multifaceted use of liquid biopsy to the management of early disease.

Letizia Pontolillo, Lorenzo Gerratana, Carolina Reduzzi.

Keywords: cell-free DNA; circulating tumor DNA (ctDNA); early detection; liquid biopsy; minimal residual disease (MRD)

DOI: https://doi.org/10.3389/fonc.2026.1879673

Cancer. 2026 Jun 15. 132(12): e70448

The evolving landscape and clinical utility of circulating tumor DNA across the spectrum of urothelial carcinoma: A systematic review and framework for clinical integration.

Sanchit Mehta, Michael Weinfeld, Charbel Hobeika, Natalie Reizine, Karine Tawagi.

Urothelial carcinoma (UC) is a significant global health challenge with heterogeneous clinical presentations from nonmuscle-invasive to metastatic disease. Circulating tumor DNA (ctDNA) has emerged as promising noninvasive biomarker for risk classification, treatment monitoring and recurrence detection. Systematic searches of PubMed identified 390 articles; 61 met inclusion criteria for plasma ctDNA analysis in UC. Independent dual screening, Joanna Briggs Institute assessment, and stratification by disease stage (nonmuscle-invasive bladder cancer [NMIBC], muscle-invasive bladder cancer [MIBC], metastatic urothelial carcinoma [mUC], and upper tract urothelial carcinoma [UTUC]) were performed. Simple pooled detection rates were calculated. ctDNA detection rates increased with disease advancement: NMIBC (53.2%), MIBC (47.6%), mUC (85.9%), and UTUC (50.5%). TERT promoter mutations predominated, followed by genomic alterations in TP53. Assays varied widely across studies with next-generation sequencing (22.4%) being most common. In NMIBC, ctDNA enabled risk stratification and recurrence detection. In MIBC, IMvigor010 demonstrated patients with positive ctDNA had worse overall survival (OS) (hazard ratio, 6.3); IMvigor011 showed that patients with negative ctDNA managed without adjuvant therapy had excellent outcomes (98% OS at 18 months). Post-surgical monitoring achieved 94%-100% sensitivity for recurrence with 96- to 131-day lead times. In mUC, KEYNOTE-361 showed ctDNA reductions at 6 weeks predicted improved OS (p < 10-4), whereas fibroblast growth factor receptor 3 mutations tracked resistance. Preoperative ctDNA fraction >2% in UTUC predicted worse OS (p < 10-3). ctDNA is a critical precision oncology tool in UC management, with TERT mutations as the predominant alteration. Stage-tailored strategies are emerging, including risk assessment in NMIBC, refining adjuvant decisions in MIBC, and treatment monitoring in mUC. Integration of ctDNA-guided approaches should proceed alongside prospective validation to ensure safe and effective adoption.

Keywords: ctDNA; liquid biopsy; molecular residual disease; precision oncology; prognostic biomarker; urothelial carcinoma

DOI: https://doi.org/10.1002/cncr.70448