bims-ovdlit 2025-11-30 papers

Issue of 2025–11–30
five papers selected by
Lara Paracchini, Humanitas Research

bioRxiv. 2025 Nov 03. pii: 2025.10.31.685873. [Epub ahead of print]

Rete Ovarii Epithelial Cells as an Unappreciated Cell of Origin for Pelvic and Ovarian High-Grade Serous Carcinoma.

Cheng Wang, Peichao Chen, Xingeng Zhao, Jinpeng Ruan, Xiangmin Lv, Jiyuan Liu, Rui Xu, Kazi Islam, Hongbo Wang, Davie Shi, Madelyn L Moness, Brianna Carbajal, Gunjan Kumar, Olukemisola A Abioye, Jeniffer McKey, John S Davis.

Over the past two decades, converging clinicopathologic, molecular, and evolutionary evidence has established that pelvic and ovarian high-grade serous carcinoma (HGSC) originates predominantly from tubal-type epithelia rather than the ovarian surface epithelium. Consequently, Fallopian tube secretory epithelial cells are widely recognized as the principal cell of origin for HGSC. However, the female reproductive tract contains additional tubular epithelial networks whose potential contributions to HGSC pathogenesis remain unexplored. Here, we identify the rete ovarii (RO), a complex network of intra- and extra-ovarian tubules located within the ovarian hilus and mesovarium, as an alternative candidate tissue of origin for HGSC. We demonstrate that genetic and genomic alterations in rete ovarii epithelial cells (ROECs) can drive their malignant transformation, giving rise to tumors that closely recapitulate the histologic and molecular characteristics of human HGSC. Spatially resolved single-cell transcriptomic analyses of tumors derived from Brca/Trp53/Pten-deficient ROECs (BTP-RO) reveal distinct invasive and immunosuppressive molecular programs. These findings establish ROECs as a previously unrecognized cell of origin for HGSC, expanding the landscape of potential precursor populations beyond the Fallopian tube. The RO-based HGSC model provides a powerful framework for developing origin-informed prevention strategies, early detection approaches, and targeted therapeutics.

DOI: https://doi.org/10.1101/2025.10.31.685873

BMC Cancer. 2025 Nov 25. 25(1): 1816

Cell-free DNA methylation and fragmentomics-based liquid biopsy for accurate esophageal cancer detection.

Jingyun Wang, Wenjing Zhang, Haohao Li, Yiting Wang, Jian Qi, Jinfu Nie.

BACKGROUND: Cell-free DNA is a promising source of biomarkers for early cancer detection and carries tumor-driven methylation and fragmentation features that have achieved good diagnostic efficacy across various cancers. However, there were no studies that detected both of them for esophageal cancer diagnosis.
METHODS: In this study, we analyzed the cfDNA methylation and fragmentation markers for accurate esophageal cancer detection. Using cfMeDIP-seq, we profiled 145 plasma samples from healthy controls and esophageal cancer patients. We used multiple algorithms to identify cfDNA methylation markers and fragmentation markers to evaluate the efficacy of early esophageal cancer detection.
RESULTS: Finally, we identified 25 cfDNA methylation and fragmentation markers and constructed a machine-learning model, which achieved a sensitivity of 99% and specificity of 97.82% in an independent cohort. These results indicate that methylation and fragmentomics biomarkers based on cfMeDIP-seq can accurately distinguish esophageal cancer patients from non-tumor controls.
CONCLUSION: Our study based on cfMeDIP-seq highlights the efficacy of cfDNA methylation and fragmentation histology markers in diagnosing esophageal cancer and provides a direction for subsequent research.

Keywords: Cancer early detection; Cell-free DNA; Esophageal cancer; Fragmentomics; Methylation; cfMeDIP-seq

DOI: https://doi.org/10.1186/s12885-025-15150-4

Am J Clin Exp Immunol. 2025 ;14(5): 262-266

Cell-free DNA fragmentomics as a non-invasive tool for predicting pathologic response in colorectal cancer.

Wenshi Hu, Guoyan Li, Wanyu Dong, Yaojuan Lu, Zhou Li, Qiping Zheng.

Despite advances in screening and therapy, colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, underscoring the need for early detection and for predicting treatment efficacy. This review highlights circulating cell-free DNA (cfDNA) fragmentomics as a promising non-invasive approach for tumor detection and disease monitoring. We focus on fragmentomic features - such as fragment size distributions, fragment-end motifs, and epigenetic signals - which, when integrated into machine-learning models, have shown strong performance in distinguishing patients with CRC from healthy controls. Emerging evidence indicates that, these signatures may support early-stage detection, track disease progression, and predict pathologic complete response (pCR), thereby enabling more personalized treatment strategies. We also discuss the potential role of fragmentomics in non-operative management, including "watch-and-wait" approaches. However, important gaps remain in clinical translation; prospective trials and standardized assays/analysis pipelines are required to validate these findings and define their real-world utility.

Keywords: Cell-free DNA; colorectal cancer; fragmentomics; non-invasive

DOI: https://doi.org/10.62347/YSQL3793

Int J Mol Sci. 2025 Nov 19. pii: 11180. [Epub ahead of print]26(22):

Spectrum and Impact of Mitochondrial DNA Mutations in Ovarian Cancer.

Samantha Su Ping Low, Laura Greaves, Ryan Silk, Colin A Semple, Charlie Gourley.

Mitochondrial DNA (mtDNA) mutations are prevalent across cancer genomes, and growing evidence implicates their multifaceted role in energy metabolism with tumorigenesis. Ovarian cancer, in particular, demonstrates high mtDNA copy numbers and increased incidences of truncating and missense mtDNA mutations, with heteroplasmy levels predictive of prognosis. This review provides a comprehensive description of published mtDNA sequencing data in ovarian cancer, the majority being high-grade serous samples, encompassing both coding and non-coding regions. MtDNA mutations within non-coding regions, such as the D-loop control region, can affect mtDNA replication and transcription, hence affecting overall mtDNA copy numbers, while mtDNA mutations within coding regions can directly impact respiratory complex function and downstream metabolic pathways. MtDNA mutations may serve as clinically valuable diagnostic biomarkers for ovarian cancer and predictors for chemoresistance. We also explore ongoing efforts to deepen our understanding of mitochondrial oncogenetics through the creation of novel cancer models enabled by mitochondrial gene editing techniques. Developing robust human ovarian cancer cell models will be critical to elucidate mechanistic and phenotypic consequences of mtDNA mutations, assess drug response and resistance and identify new therapeutic targets to advance precision oncology in this emerging field.

Keywords: gene editing; heteroplasmy; mitochondrial DNA; ovarian cancer; somatic mutations

DOI: https://doi.org/10.3390/ijms262211180