bims-fragic 2026-03-08 papers

Issue of 2026–03–08
three papers selected by
Laura Mannarino, Humanitas Research

EMBO Mol Med. 2026 Mar 06.

Cell-free DNA methylome and fragmentome analysis for relapse monitoring of Ewing sarcoma.

Sophie A Richardson, Aram Safrastyan, Mina Karimpour, Gayatri Gulati, Patrick J B Harker, Alan Redfern, Simon P Pearce, Vsevolod J Makeev, Bernadette Brennan, Alexander T J Lee, Alexandra Clipson, Steven M Hill, Caroline Dive, Dominic G Rothwell, Martin G McCabe, Florent Mouliere.

Liquid biopsies and cell-free DNA (cfDNA) offer minimally invasive methods for the diagnosis and monitoring of Ewing Sarcoma (EwS). EwS have a low tumour mutational burden and their detection with plasma cfDNA is challenging. We hypothesised that analysing the cfDNA methylome and fragmentome could enhance sensitivity for detecting EwS and identifying disease recurrence. Using T7-MBD-seq, we conducted whole-genome and methylome sequencing of cfDNA from 87 serial samples of 23 patients with EwS and 3 patients with CIC-rearranged sarcoma (CIC). With EwingSign, a new machine learning model, we identified EwS or CIC in a test set for 11 out of 16 patients at diagnosis and 15 out of 18 clinically confirmed relapse events. 0 out of 24 non-cancer controls (NCC) were detected positive with EwingSign. When combined with global and regional fragmentome analysis, all 18 relapse cases were detected, with 15/18 detected by 2 or more modalities, and 1 out of 24 NCC was detected by one modality. These findings indicate that cfDNA methylome and fragmentome analysis, if validated in a larger cohort, could improve disease detection, monitoring and relapse identification in patients with EwS.

Keywords: Cell-Free DNA; Ewing Sarcoma; Fragmentomics; Liquid Biopsy; Methylome

DOI: https://doi.org/10.1038/s44321-026-00396-7

Neurol Res. 2026 Mar 02. 1-11

The correlation between circulating DNA fragments, inflammation, oxidative stress biomarkers, and progressive multiple sclerosis: a case-control study.

Run Li, Li Yang, Juan Yang, Min Ouyang, Kaihui Jin.

OBJECTIVE: Cell-free DNA (cfDNA) is increasingly used in clinical diagnostics; however, its role in progressive multiple sclerosis (PMS) remains underexplored. This study aimed to investigate the relationship between cfDNA characteristics and disease status in PMS by analyzing cfDNA concentration and fragment size, along with biomarkers of inflammatory and oxidative stress.
METHODS: A case-control study was conducted involving 95 PMS patients and 95 matched healthy controls. Based on the 2017 McDonald criteria, PMS patients were further classified into secondary PMS (SPMS, n = 73) and primary PMS (PPMS, n = 22) groups. We measured and compared the levels of cfDNA, inflammatory markers - including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) - and oxidative stress indicators, such as malondialdehyde (MDA), total antioxidant capacity (T-AOC), glutathione (GSH), and catalase (CAT).
RESULTS: Significant differences were observed between PMS patients and controls in cfDNA content, fragment size, inflammatory indices, and oxidative stress markers (all p < 0.001). Furthermore, PPMS patients exhibited higher cfDNA content, greater fragment size, and elevated levels of SII, MDA, and CAT compared to SPMS patients (all p < 0.01). CfDNA content was positively correlated with SII (r = 0.274, p = 0.007), MDA (r = 0.267, p = 0.009), and CAT (r = 0.255, p = 0.013). ROC analysis indicated that both cfDNA content (AUC = 0.781) and fragment size (AUC = 0.712) had diagnostic value for PPMS, and their combination yielded the highest efficacy (AUC = 0.823, p < 0.001).
CONCLUSIONS: CfDNA parameters are significantly altered in PMS patients and correlate with inflammatory and oxidative stress markers. These findings suggest that cfDNA could serve as a promising biomarker for the early diagnosis and stratification of PMS.

Keywords: Circulating DNA; inflammatory factors; liquid biopsy; oxidative stress biomarkers; progressive multiple sclerosis

DOI: https://doi.org/10.1080/01616412.2025.2606230

Nat Genet. 2026 Mar 02.

Harnessing genomics for early cancer detection, risk stratification and prevention.

Muxin Gu, Woody Z Zhang, Rebecca C Fitzgerald, Alexander M Frankell, George S Vassiliou.

Therapeutic advances have improved cancer outcomes, but early-stage detection remains the single most important determinant of favorable prognoses across many cancer types. Cancer genomics has yielded detailed maps of somatic mutation and methylation patterns characteristic of different cancers, enabling the development of assays to detect mutation-bearing tumor-derived DNA in tissue biopsies, blood and other body fluids at the earliest stages of disease. In parallel, it has also become clear that small clones bearing cancer-associated mutations arise commonly in histologically normal tissues, a phenomenon that becomes universal in proliferative tissues with age but leads to cancer in only a small minority of individuals. This review article outlines established strategies for early cancer detection and highlights emerging insights into the genetics of precancerous mutant clones that have led to the recent development of prognostic frameworks for identifying high-risk individuals, making it increasingly possible to intercept evolving cancer at a premalignant or early malignant stage, when interventions are most effective.

DOI: https://doi.org/10.1038/s41588-026-02505-1