bims-fragic 2025-07-20 papers

Issue of 2025–07–20
two papers selected by
Laura Mannarino, Humanitas Research

PLoS One. 2025 ;20(7): e0327483

Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse.

Ruiqing Fu, He Amy Su, Yi Zhao, Yafei Tian, Hongyan Chen, Daru Lu.

Cell-free DNA (cfDNA) is increasingly studied for its diverse applications in non-invasive detection. Non-randomly cleaved by nucleases and released into the bloodstream, cfDNA exhibits a variety of intrinsic fragmentation patterns indicative of cell status. Particularly, these fragmentation patterns have recently been demonstrated to be effective in predicting cancer and its tissue-of-origin, owing to increased variation of fragmentation features observed in tumor patients. However, there remains a lack of detailed exploration of altered cfDNA fragmentation profiles in tumors, which consist of a mixture of both non-tumor cfDNA and circulating tumor DNA (ctDNA). Hence, we leveraged the human tumor cell line-derived xenograft (CDX) mouse model, where different tumor cell lines were implanted into different anatomical sites, to isolate pure ctDNA and separately investigate the fragment properties of CDX-cfDNA and ctDNA. We found an enrichment of short cfDNA fragments in both CDX-cfDNA and ctDNA compared to normal plasma cfDNA, with more elevated short fragments in ctDNA. Moreover, the CDX-cfDNA fragmentation features distinguished between CDX models of different tumor cell lines, while the ctDNA fragmentation features conversely discriminate between CDX models of different anatomical sites. The results suggested that both non-tumor cfDNA and ctDNA contribute to the increased variation observed in tumors, and that cfDNA fragmentation may be highly variable and susceptible to regulations by both original cells and cells within the local niche.

DOI: https://doi.org/10.1371/journal.pone.0327483

Expert Rev Mol Diagn. 2025 Jul 14. 1-19

Smaller, cheaper, faster: where next for liquid biopsies?

Valerio Gristina, Francesco Pepe, Francesca Rita Ogliari, Tancredi Didier Bazan Russo, Andrea Gottardo, Gianluca Russo, Lorena Incorvaia, Juliette Aimee Guerry, Pasquale Pisapia, Claudia Scimone, Lucia Palumbo, Antonio Galvano, Giuseppe Badalamenti, Viviana Bazan, Giancarlo Troncone, Antonio Russo, Umberto Malapelle.

INTRODUCTION: Liquid biopsy (LB) has shifted the paradigm in cancer diagnosis and management, offering a minimally invasive and dynamic approach to understanding tumor biology. Advanced next-generation sequencing (NGS) technologies have significantly improved the accuracy of LB results, enhancing both its analytical and clinical validity. However, tissue biopsy (TB) remains the gold standard for molecular analysis, often negatively impacting the molecular profiling of tumor patients owing to inadequate tissue samples, or lack thereof.
AREAS COVERED: In this scenario, LB has become a dynamic and easily-to-handle, integrative source of nucleic acids, filling the gap in tissue sample availability for molecular profiling. Moreover, cost-effectiveness analyses have also shown that when LB is correctly applied to clinical settings, healthcare spending can be optimized, enabling an increase in quality-adjusted life years at an affordable cost.
EXPERT OPINION: While LB has the potential to reduce the need for invasive TB and expedite treatment decisions, its cost-effectiveness hinges on long-term clinical outcomes and healthcare resource utilization. In this scenario, 'new era platforms' endowed with advanced liquid handling technologies could not only improve its efficiency and reduce costs but also enable higher-throughput experiments with much larger sample sizes.

Keywords: Liquid biopsy; NGS; cost-effectiveness; diagnostic accuracy; solid tumors

DOI: https://doi.org/10.1080/14737159.2025.2534961