bims-ovdlit 2025-01-26 papers

Issue of 2025–01–26
three papers selected by
Lara Paracchini, Humanitas Research

Front Oncol. 2024 ;14 1495753

The relationship between HYDIN and fallopian tubal cilia loss in patients with epithelial ovarian cancer.

Yuanli Guo, Xinxin He, Junfeng Liu, Yanming Tan, Chao Zhang, Shan Chen, Sheng Zhang.

Introduction: Primary cilia play an important role in the development of cancer by regulating signaling pathways. Several studies have demonstrated that women with BRCA mutations have, on average, 50% fewer ciliated cells compared with general women. However, the role of tubal cilia loss in the development of epithelial ovarian cancer (EOC) remains unclear. Few specific studies have been found in linking HYDIN, a ciliary defect associated gene that encodes HYDIN axonemal central pair apparatus protein, which is involved in the transduction of Hedgehog (Hh) signal and is considered a cancer associated antigen, to ovarian cancer. Therefore, our study aimed to investigate the correlation between HYDIN gene mutations and tubal cilia loss in EOC.
Methods: A whole exome sequencing (WES), immunohistochemistry (IHC), western blot, and reverse transcription quantitative (RT q) PCR were performed in 80 patients with EOC and 50 cases of non ovarian cancer to detect the mutations and expression of tubal ciliary marker, ciliary morphology, and abnormal rate.
Results: We found that the incidence of tubal cilia loss was higher in EOC group with decreased expression of HYDIN compared with the control group (P<0.05).
Discussion: This study suggests that tubal ciliary loss is evident in epithelial fallopian tube carcinoma, and ciliary cells may be involved in the occurrence and development of EOC, and cilia-related gene HYDIN is expected to be a tumor marker for epithelial ovarian cancer.

Keywords: HYDIN; cilia; epithelial ovarian cancer; fallopian tubes; marker

DOI: https://doi.org/10.3389/fonc.2024.1495753

J Mol Diagn. 2025 Jan 17. pii: S1525-1578(25)00011-X. [Epub ahead of print]

Optimization of pre-analytical handling to maintain DNA integrity in diagnostic Papanicolaou tests.

Sara Schumacher, Jacob Malchau Lauesgaard, Therese Carlsson, Anna Linder, Karin Sundfeldt.

Cell-free DNA of ovarian tumor origin can be detected in samples from the gynecologic tract. This study aims to evaluate how pre-analytical handling, and storage conditions affect DNA profile and integrity in Pap tests, to optimize its potential for detection of ovarian cancers (OC). Analysis of archived Pap tests from OC patients, kept at RT for 48h and stored at -80°C was complemented by in vitro experiments. Temperature-associated effects on DNA fragmentation were evaluated in samples stored at 4°C, -20°C or -80°C. Time-dependent DNA degradation at RT was evaluated in comparison to storage at 4°C (0-96h). Results were validated in prospectively collected Pap tests. The DNA integrity was assessed by fragment analysis. Accumulation of short DNA fragments was observed in archived Pap tests from OC patients. In vitro, fragments of 100-350bp increased 11.5-fold within 48h at RT compared to 1.7-fold when stored at 4°C. Consistent with the in vitro findings, prospectively collected samples showed reduced fragmentation when stored at 4°C compared to RT (p=0.007). Long-term storage at 4°C had a significant negative effect on DNA stability (p=0.013), while freezing slowed down fragmentation. This study highlights the need for optimization of pre-analytical handling for cfDNA analysis. Immediate storage at 4°C after sampling markedly reduces DNA degradation suggesting a simple way to decrease unwanted fragmentation for cfDNA analysis in Pap tests.

Keywords: DNA fragmentation; Pap test; cell-free DNA (cfDNA); gynecologic cancer

DOI: https://doi.org/10.1016/j.jmoldx.2024.12.008

Nat Rev Genet. 2025 Jan 21.

Diversity and consequences of structural variation in the human genome.

Ryan L Collins, Michael E Talkowski.

The biomedical community is increasingly invested in capturing all genetic variants across human genomes, interpreting their functional consequences and translating these findings to the clinic. A crucial component of this endeavour is the discovery and characterization of structural variants (SVs), which are ubiquitous in the human population, heterogeneous in their mutational processes, key substrates for evolution and adaptation, and profound drivers of human disease. The recent emergence of new technologies and the remarkable scale of sequence-based population studies have begun to crystalize our understanding of SVs as a mutational class and their widespread influence across phenotypes. In this Review, we summarize recent discoveries and new insights into SVs in the human genome in terms of their mutational patterns, population genetics, functional consequences, and impact on human traits and disease. We conclude by outlining three frontiers to be explored by the field over the next decade.

DOI: https://doi.org/10.1038/s41576-024-00808-9