bims-ovdlit 2025-09-07 papers

Curr Treat Options Oncol. 2025 Sep 05.

From Fallopian Tube to Ovarian Cancer: Understanding the Evaluation and Management of Serous Tubal Intraepithelial Carcinoma Lesions.

Vinita Popat, Ernest Han.

OPINION STATEMENT: Ovarian cancer, particularly high-grade serous carcinoma (HGSC), remains a leading cause of mortality in gynecologic oncology. Emerging research identifies serous tubal intraepithelial carcinoma (STIC) as a precursor lesion in many HGSC cases, highlighting its role in ovarian cancer pathogenesis and prevention. Management of STIC is challenging, as there is only limited data available to guide clinical decision-making. For average-risk women, opportunistic salpingectomy is increasingly being adopted during routine procedures such as hysterectomy or cesarean section. This intervention has demonstrated significant potential in reducing ovarian cancer incidence while maintaining safety and feasibility. For high-risk individuals, particularly BRCA mutation carriers, risk-reducing salpingo-oophorectomy (RRSO) remains the gold standard. RRSO significantly lowers ovarian cancer risk, though alternative approaches like salpingectomy alone or radical fimbriectomy are under investigation to preserve ovarian function in younger patients. To improve STIC detection, SEE-FIM pathology protocol is recommended when patients are undergoing risk-reducing surgery to prevent ovarian cancer, but challenges such as diagnostic variability and limited data persist. When STIC is detected incidentally, management varies based on risk factors and lesion characteristics. Genetic counseling and testing are essential when STIC is identified, as hereditary predisposition may guide further management. Surgical management is advised for cases of STIC with microinvasive carcinoma, but routine use of surgical management for STIC is not clearly defined in the literature. Bilateral oophorectomy is generally recommended when STIC is identified, and adnexal structures have not yet been removed. Chemotherapy is not recommended for treatment of STIC. Surveillance is suggested when STIC has been diagnosed, but there are no set guidelines as to the frequency and type of monitoring. Future directions include refining molecular profiling to predict progression and conducting randomized studies to establish evidence-based guidelines. Multidisciplinary collaboration is essential to optimize prevention and treatment, ultimately reducing HGSC incidence and improving patient outcomes.

Keywords: BRCA; High grade serous cancer; Ovarian cancer; Peritoneal cancer; Risk reducing salpingo-oophorectomy; STIC

DOI: https://doi.org/10.1007/s11864-025-01346-0

medRxiv. 2025 Aug 28. pii: 2025.08.25.25333715. [Epub ahead of print]

Integration of cell-type resolved spatial proteomics and transcriptomics reveals novel mechanisms in early ovarian cancer.

High-grade serous carcinoma (HGSC) is the most common ovarian cancer subtype, typically diagnosed at late stages with poor prognosis. Understanding early molecular events driving HGSC progression is crucial for timely detection and development of effective treatment strategies. We performed and integrated spatial cell-type resolved proteomics and paired transcriptomics across 25 women with precursor lesions of the fallopian tube and/or HGSC. Epithelial cell signatures revealed early activation of SUMOylation machinery, increased ATR and Wnt signaling, and enhanced MHC-I antigen presentation along the disease trajectory. The stroma exhibited extracellular matrix remodeling and interferon-mediated inflammation. Serous tubal intraepithelial carcinomas (STICs) in cancer patients contained a pro-coagulative signature and reduced APOA1/2 compared to STICs in individuals without cancer. We functionally established important roles of epithelial-derived TRIP13 and SUMOylation, and cancer-associated fibroblast-derived SULF1 and BGN in HGSC progression. These findings provide unique molecular insights into HGSC pathogenesis and identify potential new therapeutic targets for intervention.

DOI: https://doi.org/10.1101/2025.08.25.25333715

Lancet Oncol. 2025 Sep;pii: S1470-2045(25)00340-7. [Epub ahead of print]26(9): 1142-1143

Prevention and empowerment: cultural influences on prophylactic surgical decisions among BRCA mutation carriers in east Asia.

Teng Qi, Hanqing Zhao.

DOI: https://doi.org/10.1016/S1470-2045(25)00340-7

Int J Gynaecol Obstet. 2025 Sep;171 Suppl 1 6-35

Cancer of the ovary, fallopian tube, and peritoneum: 2025 update.

Malte Renz, Michael Friedlander, Jonathan S Berek.

In 2014, FIGO's Committee for Gynecologic Oncology revised the staging of ovarian cancer, incorporating ovarian, fallopian tube, and peritoneal cancer into the same system. Most of these malignancies are high-grade serous carcinomas (HGSCs). Stage IC is now divided into three categories: IC1 (surgical spill), IC2 (capsule ruptured before surgery or tumor on ovarian or fallopian tube surface), and IC3 (malignant cells in the ascites or peritoneal washings). The updated staging includes a revision of Stage IIIC based on spread to the retroperitoneal lymph nodes alone without intraperitoneal dissemination. This category is now subdivided into IIIA1(i) (metastasis ≤10 mm in greatest dimension) and IIIA1(ii) (metastasis >10 mm in greatest dimension). Stage IIIA2 is now "microscopic extrapelvic peritoneal involvement with or without positive retroperitoneal lymph node" metastasis. This review summarizes the genetics, surgical management, chemotherapy, and targeted therapies for epithelial cancers, including the treatment of ovarian germ cell and stromal malignancies.

Keywords: FIGO cancer report; cancer staging; chemotherapy; fallopian tube; ovary; peritoneum

DOI: https://doi.org/10.1002/ijgo.70282

Nat Genet. 2025 Sep 04.

DNA methylation influences human centromere positioning and function.

Maintaining the epigenetic identity of centromeres is essential to prevent genome instability. Centromeres are epigenetically defined by the histone H3 variant CENP-A. Prior work in human centromeres has shown that CENP-A is associated with regions of hypomethylated DNA located within large arrays of hypermethylated repeats, but the functional importance of these DNA methylation (DNAme) patterns remains poorly understood. To address this, we developed tools to perturb centromeric DNAme, revealing that it causally influences CENP-A positioning. We show that rapid loss of methylation results in increased binding of centromeric proteins and alterations in centromere architecture, leading to aneuploidy and reduced cell viability. We also demonstrate that gradual centromeric DNA demethylation prompts a process of cellular adaptation. Altogether, we find that DNAme causally influences CENP-A localization and centromere function, offering mechanistic insights into pathological alterations of centromeric DNAme.

DOI: https://doi.org/10.1038/s41588-025-02324-w

Nature. 2025 Sep 03.

Single-cell transcriptomic and genomic changes in the ageing human brain.

Ailsa M Jeffries, Tianxiong Yu, Jennifer S Ziegenfuss, Allie K Tolles, Christina E Baer, Cesar Bautista Sotelo, Yerin Kim, Zhiping Weng, Michael A Lodato.

Over time, cells in the brain and in the body accumulate damage, which contributes to the ageing process1. In the human brain, the prefrontal cortex undergoes age-related changes that can affect cognitive functioning later in life2. Here, using single-nucleus RNA sequencing (snRNA-seq), single-cell whole-genome sequencing (scWGS) and spatial transcriptomics, we identify gene-expression and genomic changes in the human prefrontal cortex across lifespan, from infancy to centenarian. snRNA-seq identified infant-specific cell clusters enriched for the expression of neurodevelopmental genes, as well as an age-associated common downregulation of cell-essential homeostatic genes that function in ribosomes, transport and metabolism across cell types. Conversely, the expression of neuron-specific genes generally remains stable throughout life. These findings were validated with spatial transcriptomics. scWGS identified two age-associated mutational signatures that correlate with gene transcription and gene repression, respectively, and revealed gene length- and expression-level-dependent rates of somatic mutation in neurons that correlate with the transcriptomic landscape of the aged human brain. Our results provide insight into crucial aspects of human brain development and ageing, and shed light on transcriptomic and genomic dynamics.

DOI: https://doi.org/10.1038/s41586-025-09435-8